LAURIE H. GLIMCHER, MD President and CEO, Dana Farber Cancer Institute CEO, Dana-Farber/Partners Cancer Care Trustee, Dana-Farber/Children’s Hospital Cancer Care Professor of Medicine, Harvard Medical School

Biography Dr. Glimcher received a bachelor's degree, magna cum laude, from Radcliffe College and a medical degree, cum laude, from Harvard Medical School. Immediately prior to assuming the presidency of the Institute, Dr. Glimcher served as the Stephen and Suzanne Weiss Dean and Professor of Medicine of Weill Cornell Medical College in New York City, and Provost for Medical Affairs of Cornell University. From 1991-2011, Dr. Glimcher was the Irene Heinz Given Professor of Immunology at the Harvard School of Public Health, where she was director of the Division of Biological Sciences, and Professor of Medicine at Harvard Medical School, where she headed one of the top immunology programs in the world.

Research As an immunologist, her primary research interests are elucidating the molecular pathways that regulate the immune system, critical for both the development of protective immunity and for the pathophysiologic immune responses underlying autoimmune, infectious and malignant diseases. She is a Fellow of the American Academy of Arts and Sciences, a Member of the National Academy of Medicine and a Member of the National Academy of Sciences. She sits on the Corporate Board of Directors of the Bristol-Myers Squibb Pharmaceutical Corporation and the Waters Corporation. Interests: Immunology, Autoimmune, Infections, and Malignant Diseases Publications: View publications in PubMed

KENNETH C. ANDERSON, MD Program Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics Institute Physician Kraft Family Professor of Medicine, Harvard Medical School

Biography Dr. Anderson graduated from Johns Hopkins Medical School, trained in internal medicine at Johns Hopkins Hospital, and completed hematology, medical oncology, and tumor immunology training at Dana-Farber Cancer Institute. He serves as chief of the Division of Hematologic Neoplasia, director of the Jerome Lipper Multiple Myeloma Center, and vice chair of the Joint Program in Transfusion Medicine at Dana-Farber. Research Dr. Anderson’s laboratory efforts focus on translational research in multiple myeloma. His lab characterizes factors in the marrow

microenvironment which allow tumor cell homing, growth and resistance to apoptosis in the marrow millieu in order to devise therapies which interrupt these processes. Dr. Anderson is delineating signaling cascades mediating growth, death, and resistance to apoptosis in myeloma cells in order to devise novel treatment strategies which interrupt growth, trigger apoptosis, and overcome drug resistance. Finally, his efforts are directed to delineate mechanisms for enhancing allogeneic and autologous immunity to myeloma cells in order to derive related novel vaccination and adoptive immunotherapy treatments. Interests: Multiple myeloma, Stem cell/bone marrow transplant Publications: View publications in PubMed

SCOTT A. ARMSTRONG, MD, PhD Chairman, Department of Pediatric Oncology Associate Chief, Division Hematology/Oncology, Boston Children's Hospital David G. Nathan Professor of Pediatrics, Harvard Medical School School

Biography Dr. Armstrong earned his medical degree and his PhD from University of Texas Southwestern Medical School in 1996. After internship and residency training with the Boston Combined Residency Program (BCRP) at Boston Medical Center and Boston Children’s Hospital, he completed a hematology/oncology fellowship at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dr. Armstrong became the Chairman of the Department of Pediatric Oncology at Dana-Farber Cancer Institute in July 2016. He also serves as Associate Chief of the Division of Hematology/Oncology at Boston Children’s Hospital. He was previously the Director of the Center for Epigenetics Research at Memorial Sloan Kettering Cancer Center and

Professor of Pediatrics at the Weill Cornell Medical College. Research The Armstrong laboratory is focused on the mechanisms of cancer development with a focus on leukemia. One major interest in the lab is the relationship between leukemia, normal hematopoietic stem cells and the various hematopoietic cells of origin of leukemia. The lab is also studying the role of histone modifications and chromosome structure as a critical initial step in cancer development and how these mechanisms can be targeted therapeutically. This work has prompted a search for therapies that can reverse this process and eradicate cancer cells, and has led to the development of new therapies that are now being tested in patients. He was previously the Director of the Center for Epigenetics Research at Memorial Sloan Kettering Cancer Center and Professor of Pediatrics at the Weill Cornell Medical College where he initiated a research program in cancer epigenetics that has made significant contributions to the understanding of cancer biology. The major focus of his career has been on delineating the biology of childhood cancers, particularly leukemia. His work has led to the development of new therapeutic approaches for multiple types of cancer that are now being tested. Interests: Hematologic malignancies Publications: View publications in PubMed

DAVID A. BARBIE, MD Physician Assistant Professor of Medicine, Harvard Medical School

Biography Dr. Barbie received his MD degree from Harvard Medical School in 2002. His residency training was in internal medicine at Massachusetts General Hospital, where he also served as chief resident in internal medicine. He completed his fellowship training in medical oncology in the Dana-Farber/Partners CancerCare program. Research Dr. Barbie’s interest as a medical oncologist and cancer biologist is to identify novel targets for cancer therapy. Specifically, he has focused on lung cancer clinically with a particular interest in targeting KRAS mutations, which have remained refractory to current

therapies. Recently, Dr. Barbie’s laboratory discovered that a kinase inhibitor, momelotinib, inhibits TBK1 and JAK signaling and has activity in mouse models of Kras-driven lung cancer. Based on these findings, they have opened a trial together with Gilead Sciences combining momelotinib with the MEK inhibitor trametinib in treatment refractory KRAS mutant lung cancer. His overall goal is to continue this effort clinically and in the lab to refine combination therapy for KRAS-driven lung cancer and improve outcomes for this challenging disease. Interests: Lung cancer, Translational oncology, KRAS targeted therapy Publications: View publications in PubMed

ADAM BASS, MD Physician Assistant Professor of Medicine, Harvard Medical School

Biography Dr. Bass obtained his undergraduate degree from Amherst College and his MD degree at Duke University School of Medicine then pursued clinical training in internal medicine at the Massachusetts General Hospital and medical oncology at the Dana-Farber/Partners Cancer Center. At the completion of his clinical training, he was a post-doctoral fellow with Dr. Matthew Meyerson at both the Dana-Farber Cancer Institute and Broad Institute. Dr. Bass is an assistant professor of medicine at Harvard Medical School, a physician/scientist at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital and also is an associate member of the Broad Institute. Research

In The Bass lab, Dr. Bass and his colleagues bring together expertise in modern genomics, experimental/functional biology and clinical medicine. They study the cancer genome to elucidate key biological processes and therapeutic vulnerabilities in carcinomas arising in the GI tract (stomach, esophageal and colorectal) and also squamous cell cancer of the lung (highly related to esophageal squamous cell cancer). Working closely with the Broad Institute and The Cancer Genome Atlas projects, which he co-chairs, Dr. Bass is at the forefront of several major initiatives to interrogate the genomes of these cancers, working to define the spectrum of alterations and the most likely critical genes in these tumors. He then brings key genes into his laboratory to study their contribution to cancer in more depth. In parallel, Dr. Bass and his lab are developing systematic approaches to allow them to efficiently evaluate the complex myriad of alterations that exist in these tumors to help define those which are critically important and should be prioritized for focused follow-up. In pre-clinical models, the Bass lab is beginning to test therapeutic approaches for cancers driven by specific genetic alterations, moving closer to the era when genomic profiling of each patient’s tumor will be an integral factor in guiding cancer care. His focus on gastrointestinal oncology brings the power of genomics to a group of very common and deadly tumors that have not had the scientific attention they warrant. Interests: Genomic Characterization and Pathogenesis of Gastrointestinal Cancers Publications: View publications in PubMed Lab: http://bass.dfci.harvard.edu/index.html

RAMEEN BEROUKHIM, MD, PhD Physician Assistant Professor of Medicine, Harvard Medical School

Biography Dr. Beroukhim obtained his PhD in Molecular Biology from the University of Cambridge in England and his MD from the University of California, San Francisco. He received his AB in Physics and Philosophy from University of California, Berkeley. Research Research at the Beroukhim Lab focuses on understanding the genetic changes in cancer and how these genetic changes affect cancer behavior. Dr. Beroukhim and his team have a particular focus on brain cancers, although they study many types of cancer. They have undertaken a variety of genomic approaches to profiling large numbers

of cancers, including genomic and transcriptomic characterization and high-throughput functional screens. They have also developed several computational approaches to understand these data, with an emphasis on structural alterations in cancer genomes. Dr. Beroukhim and his colleagues have used these approaches to study genomic profiles from tens of thousands of cancers across all major histologic types, including primary tumors to identify genetic alterations contributing to oncogenesis, and metastatic and recurrent tumors to study tumor evolution. They have also identified new classes of genetically determined cancer vulnerabilities such as CYCLOPS vulnerabilities on essential genes that undergo partial loss in cancer. Dr. Beroukhim’s group currently have particular interests in the following areas: 1) The use of high-throughput sequencing technologies to profile somatic genetic changes through tumor evolution in brain and other cancers. 2) The development and use of analytic methods to interpret these somatic genetic data. 3) Understanding the implications of these somatic genetic changes on cancer biology and phenotype. 4) Detecting therapeutically tractable vulnerabilities associated with these genomic alterations. Interests: Glioma, Somatic genetics of cancer, Alterations in genome structure Publications: View publications in PubMed Lab: http://beroukhimlab.dfci.harvard.edu

ALESSANDRA BIFFI, MD Director, Gene Therapy Program Associate Professor of Pediatrics, Harvard Medical School

Biography Alessandra Biffi received her medical degree from University of Milano School of Medicine and San Raffaele in Milano, Italy 1198. She went on to complete her Fellowship, Internship, and Residency at the University. Dr. Biffi is the current director of the Gene therapy Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Her previous position was in Milano, at the San Raffaele Telethon Institute for Gene Therapy where she trained and developed a Research and Clinical Unit dedicated to the treatment of lysosomal storage disorders (LSDs) by means of hematopoietic stem cell (HSC)-based approaches. She is actively involved in gene therapy trials for genetic diseases of childhood.

Research Hematopoietic stem cell (HSC) progeny can represent a vehicle for therapeutic molecule delivery to the Central Nervous System (CNS) upon transplantation in myeloablated host. This effect was demonstrated in animal models and patients affected by lysosomal storage disorders (LSDs), and it is dependent on the reconstitution of CNS myeloid cells, eventually including microglia, by the transplanted HSCs and their progeny. Dr. Biffi and her team showed that the therapeutic potential of HSC transplantation for treating NeuroDegenerative Diseases (NDDs) can be enhanced by means of i) gene transfer into the transplanted HSCs for increasing the production of therapeutic molecules delivered to the brain by transplanted HSC progeny; ii) the use of a pre-transplant conditioning aimed not only at HSC ablation from the bone marrow, but also at eliminating CNS microglia progenitors; and iii) delivery of HSCs within brain lateral ventricles, to further enhance CNS myeloid cell and microglia reconstitution by the transplanted HSCs. Dr. Biffi and her team are pursuing these strategies in the context of innovative cell and gene therapy applications for neurodegenerative LSDs employing autologous HSCs transduced with lentiviral vectors (LVs) ubiquitously expressing the therapeutic gene of interest or allogeneic HSCs in the context of myeloablated patients. They are also applying these strategies to the more frequent NDDs of adulthood, such as Amyotrophic Lateral Sclerosis (ALS) or Alzheimer’s disease. A key role has recently been attributed to microglia activation and neuro-inflammation as molecular mechanisms leading to tissue damage in NDDs and most innovative therapeutic strategies are aimed at targeting these events for therapeutic purposes. Interests: Gene therapy, Metabolic disorders, Lysosomal disorders, Hematopoietic stem cell transplantation Publications: View publications in PubMed

JENNIFER R. BROWN, MD, PhD Director, Chronic Lymphocytic Leukemia Center Institute Physician Associate Professor of Medicine, Harvard Medical School

Biography Jennifer R. Brown, MD, PhD, is the Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and an Associate Professor of Medicine at Harvard Medical School. Dr. Brown completed a B.S. and M.S. simultaneously in molecular biophysics and biochemistry (MB&B) at Yale, graduating summa cum laude with distinction in MB&B. She received her MD and PhD from Harvard Medical School in molecular genetics in 1998 and was awarded the James Tolbert Shipley Prize for research accomplishment in the graduating class. She did her internship and residency in Internal Medicine at Massachusetts General Hospital followed by a

fellowship in Hematology and Medical Oncology at Dana-Farber Cancer Institute. Dr. Brown joined the faculty of DFCI and Harvard Medical School in 2004, where she has an active clinical-translational research program in CLL. Research Dr. Brown’s particular interests include the development of novel targeted therapeutics for CLL, as well as the genomics of CLL. She has been instrumental in the clinical development of both idelalisib and ibrutinib, leading to their regulatory approvals in CLL. Her work on the somatic mutation profile of CLL is pivotal, and she is now particularly interested in the implementation of genomic technology in the clinic, including for prognosis and targeted therapy. She also has a longstanding research interest and focus on the inherited predisposition to CLL. She is an active member of the CLL Research Consortium and serves on the Alliance Leukemia and Leukemia Correlative Science Committees as well as the NIH Cancer Biomarkers Study Section. In 2014 she was the recipient of two awards from Dana-Farber Cancer Institute, the Clinical Innovation Award, as well as the George Canellos Award for Excellence in Clinical Investigation and Patient Care. She enjoys a worldwide reputation as a CLL expert and is in much demand as an international speaker. Interests: Chronic lymphocytic leukemia, Lymphoma, Stem cell/bone marrow transplant Publications: View publications in PubMed

MYLES A. BROWN, MD Physician Director, Center for Functional Cancer Epigenetics Professor of Medicine, Harvard Medical School

Biography Dr. Brown obtained his undergraduate degree in Biology from Yale University and his M.D. from the Johns Hopkins University School of Medicine. He completed training in Internal Medicine at Brigham and Women's Hospital while doing research with David Livingston at the Dana-Farber. He went on to complete training in Medical Oncology at Dana-Farber Cancer Institute and postdoctoral research with Phillip Sharp at MIT. Following the completion of his training he joined the faculty of Dana-Farber Cancer Institute and Harvard Medical School. From 2002-2010 he served as Chief of the Division of Molecular and Cellular Oncology at the Dana-Farber. In 2010 together with Shirley Liu he founded the Center for Functional Cancer Epigenetics at the Dana-

Farber. Dr. Brown was elected to The National Academy of Sciences in 2017 in recognition of his distinguished and continuing achievements in original research, one of the highest honors that a scientist can achieve. Research Dr. Brown’s research laboratory focuses on elucidating the epigenetic factors underlying the action of steroid hormones. This work has important implications both for normal physiology and for the treatment of hormone dependent malignancies including breast and prostate cancer. He is recognized for three seminal discoveries: his lab opened the steroid receptor coregulator field, illuminated the dynamic nature of receptor and coregulator interaction with the genome and elucidated the importance of epigenetically determined distant cis-regulatory steroid receptor binding sites. His contributions have uniquely deepened and altered the understanding of steroid hormone action in normal physiology and in hormone-dependent cancer. Interests: Epigenomics of hormone action Publications: View publications in PubMed Lab: https://research4.dfci.harvard.edu/brownlab/

SARA BUHRLAGE, PhD Assistant Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Assistant Professor of Cancer Biology, Dana-Farber Cancer Institute

Biography Dr. Buhrlage received her PhD in organic chemistry from University of Michigan in 2008 under the direction of Professor Anna Mapp. She then trained for two years in medicinal chemistry at the Broad Institute before joining Dana-Farber’s medicinal chemistry core as a professional track scientist. In that role she collaborated with cancer biologists and clinicians to pharmacologically validate novel targets of disease in vitro and in vivo and to study mechanisms of disease and drug resistance. Dr. Buhrlage joined the DFCI Cancer Biology and HMS Biomolecular and Cellular Pharmacology faculty in 2015. Research

The Buhrlage Laboratory utilizes chemistry, biochemistry and cellular biology to study proteostasis in cancers. Protein homeostasis, or proteostasis, is simply defined as the processes by which cells control the concentration and conformation of the proteome. The ubiquitin system in particular is critical in controlling the concentration of proteins. Ubiquitylation is a reversible post-translational modification whose most well-known and best characterized function is tagging proteins for proteolytic degradation. However, its critical role in protein activation/inactivation, localization, signal transduction and lysosomal and autophagic degradation among other cellular processes is becoming increasingly appreciated. Deubiquitinating enzymes (DUBs), an approximately 100 member family of proteases that remove the post-translational modification of ubiquitin from substrate proteins, are central to the ubiquitin system. Deubiquitinating enzymes (DUBs) have garnered significant attention as drug targets in recent years. Significant research effort from Dr. Buhrlage’s lab is focused on generating chemical tools that can be utilized to transform our understanding of normal and disease DUB biology, particularly as it pertains to protein homeostasis in cancer. Current projects include: identification of oncoprotein stabilizing DUBs, development of first-in-class inhibitors of DUBs implicated in disease, development of technologies to study the ubiquitin system, and execution of a gene family approach to identify new small molecule DUB inhibitors and scaffolds. She and her colleagues are also interested in developing small molecules that target protein-protein interactions in the ubiquitin system. Interests: Chemical Biology, Novel strategies for drug targets Publications: View publications in PubMed Lab: http://buhrlagelab.dana-farber.org/

HARVEY CANTOR, MD Baruj Benacerraf Professor, Immunology Division, Microbiology and Immunobiology, Harvard Medical School Department of Cancer Immunology & Virology, Dana Farber Cancer Institute

Biography BA, Columbia University MD, New York University School of Medicine Honorary MA, Harvard University Research Inactivation/depletion of Treg: new target A successful approach to cancer immunotherapy has depended on

depletion or blockade of CD4 Treg activity resulting in a shift in the

intratumoral Teff–Treg ratio. Dr. Cantor’s recent studies of a murine

model of melanoma indicate that blockade of CD8 Treg activity also

results in a shift in the intratumoral Teff–Treg ratio and substantially

enhanced anti-tumor immune responses. These findings have suggested several new approaches to

targeting Treg in the context of tumor immunotherapy.

1. Inactivation of Treg by targeting Helios: A strategy that targets both lineages of Treg depends on

our recent studies which indicate that (a) the Helios transcription factor is selectively expressed by

both FoxP3+ CD4 Treg and Qa-1-restricted CD8 Treg (CD122+Ly49+), and (b) Helios expression is

essential for maintenance of a stable suppressive phenotype by both regulatory T-cell lineages (Kim

et al, Science, under review).

2. Depletion of CD8+ Treg using anti-KIR antibodies: Analysis of the response to viral infection

(LCMV) and tumor growth (B16 melanoma) suggests that depletion of CD8 Treg using anti-Ly49 Abs

can enhance anti-viral and anti-tumor immune responses.

Interests: Cancer immunotherapy, Regulatory T cell inactivation (CD4, CD8), Helios transcription factor, killer cell immunoglobulin-like receptors (KIR) Publications: View publications in PubMed

ALAN D. D’ANDREA, MD Director, Susan F. Smith Center for Women's Cancers Director of the Center for DNA Damage and Repair Alvan T. & Viola D. Fuller American Cancer Society Professor of Radiation Oncology, Harvard Medical School

Biography Dr. D'Andrea received his MD in 1983 from Harvard Medical School, residency training in pediatrics at Children's Hospital of Philadelphia, and fellowship training in pediatric hematology-oncology at DFCI and Children's Hospital Boston (CHB). He completed a research fellowship at the Whitehead Institute and joined DFCI in 1990. He is scientific director of the DFCI Molecular Diagnostics Laboratory and director of the Clinical Gene Therapy Center at CHB, and was recently appointed Director, Susan F. Smith Center for Women's Cancers at DFCI. Research Dr. D’Andrea’s lab examines the molecular signaling pathways which

regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors. Dr. D’Andrea’s primary focus is the molecular pathogenesis of the human chromosome instability syndromes: Fanconi anemia (FA), ataxia-telangiectasia (AT), and Bloom syndrome (BS). FA is an autosomal-recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents. Dr. D’Andrea’s laboratory research program addresses several aspects of the Fanconi anemia signaling pathway, including (1) the assembly, transport, and structure of the FA protein complex; (2) the enzymatic monoubiquitination and deubiquitination of the D2 protein; (3) the function of the chromatin-associated FA complex in cell cycle checkpoints and homologous recombination DNA repair; and (4) the identification of novel interacting proteins in these complexes. Interests: Cancer susceptibility, Fanconi anemia, Gene therapy, Genetic risk Publications: View publications in PubMed Lab: http://www.dandrealab.org/

MATTHEW S. DAVIDS, MD, MMSc Associate Director, Center for Chronic Lymphocytic Leukemia Physician Assistant Professor of Medicine, Harvard Medical School

Biography After obtaining an A.B. in chemistry at Harvard College, Dr. Davids completed his M.D. at Yale University School of Medicine. He served as an intern, resident, and assistant chief resident in internal medicine at New York-Presbyterian Weill Cornell Medical Center and Memorial Sloan-Kettering Cancer Center in New York City. He then completed his fellowship in hematology and oncology in Dana-Farber/Partners CancerCare, and a Masters in Medical Science (MMSc) at Harvard Medical School. He is an attending physician in the Lymphoma Program of the Division of Hematologic Malignancies at Dana-Farber, an Assistant Professor of Medicine at Harvard Medical School, and is the Associate

Director of the Dana-Farber CLL Center.

Research Dr. Davids has an active translational research program in chronic lymphocytic leukemia (CLL), studying Bcl-2 biology in his laboratory and leading clinical trials to evaluate novel therapeutic strategies in patients with CLL and other hematologic malignancies. Much of his work has focused on the clinical development of the Bcl-2 inhibitor venetoclax and utilizing checkpoint blockade to enhance anti-tumor immunity in patients with hematologic malignancies who relapse post allogeneic hematopoietic cell transplantation. Dr. Davids’ laboratory utilizes the BH3 profiling technique to study the effects of novel agents such as B cell receptor inhibitors, Bcl-2 antagonists, and monoclonal antibodies on the mitochondria of CLL cells. Dr. Davids and his colleagues do ex vivo work on patient samples to devise novel combination strategies to explore in the clinic. They also study in vivo samples from patients already on clinical trials to assess the effects of these new drugs in patients. The Davids lab focuses on interrogating the mitochondrial pathway of apoptosis through BH3 profiling to predict response and resistance to these treatments, with a goal to eventually use this technique to guide therapeutic decisions. Interests: Chronic lymphocytic leukemia, lymphoma, Stem cell/bone marrow transplantation Publications: View publications in PubMed Lab: http://davidslab.dana-farber.org/

STEPHANIE DOUGAN, PhD Assistant Professor in Microbiology and Immunobiology, Dana-Farber Cancer Institute

Biography Dr. Dougan received her PhD in immunology from Harvard University in 2007 and performed postdoctoral work at the Whitehead Institute with Dr. Hidde Ploegh. While at Whitehead, she collaborated with Dr. Rudolf Jaenisch to learn somatic cell nuclear transfer and generate a panel of transnuclear mice. Stephanie Dougan joined the DFCI and Harvard faculty in 2014. Research: Preclinical Models for immunotherapy, including transnuclear and CRISPR gene-modified mice The Dougan lab generates transnuclear mouse models to explore

questions of anti-tumor immunity. Dr. Dougan’s long-term goal is to understand the complex network of cellular interactions that shape the tumor microenvironment. CD8 T cells do not occur in isolation; they operate in oligoclonal fashion amid regulatory T cells, myeloid cells, and other immune infiltrates, not to mention heterogeneous tumor cells, stroma, and vasculature. These interactions cannot be accurately modeled using xenografts, nor are they fully replicated in humanized mice that develop human leukocytes, but still face cross-species barriers with respect to immune-stromal interactions and T cell development.

The Dougan lab clones mice from a variety of tumor-infiltrating lymphocytes in order to study the effects of each lymphocyte type in isolation, and more importantly, when combined with each other and with various immune-based therapies. The technology is also used in reverse to clone mice from tumor-infiltrating Tregs as a means of determining their antigen-specificity.

Currently the lab focuses on three major tumor types: melanoma, sarcoma, and pancreatic cancer. Of these, pancreatic cancer has been the most refractory to immunotherapy. A combination of RNAseq profiling and targeted gene silencing in pancreatic-tumor specific CD8 T cells to design effective immunotherapies for pancreatic cancer. Publications: View Publications in PubMed Lab: http://douganlab.dana-farber.org/

MICHAEL J. ECK, MD, PhD Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Professor, Cancer Biology, Dana-Farber Cancer Institute

Biography Dr. Eck received his M.D. and Ph.D. from the University of Texas Southwestern Medical School in 1991. He trained as a postdoctoral fellow with Dr. Stephen Harrison at Children’s Hospital and Harvard Medical School before joining the DFCI in 1996. Dr. Eck is currently Professor of Biological Chemistry and Molecular Pharmacology at the Dana-Farber Cancer Institute and Harvard Medical School. His research focuses on the structure and regulation of tyrosine kinases in cancer and on structure-based approaches to discovery of novel inhibitors. The Eck lab also studies the structure of formin proteins and their role in assembling the actin cytoskeleton.

Research The Eck Laboratory employs biochemical and structural methods (primarily X-ray crystallography) to define the molecular interactions that underlie cytoplasmic signal transduction. Dr. Eck and his colleagues are especially interested in determining the structure of signaling complexes that underlie cancer, and in using structural approaches to facilitate development of anti-cancer drugs. Active areas of investigation include: 1) the structural biology of integrins, focal adhesion kinase (FAK), and Src-family kinases in the regulation of cytoskeletal rearrangements, 2) the cytoplasmic signaling interactions that control antigen-dependent T-cell activation, and 3) the interactions of the transcription factor Tcf4 with beta-catenin, a driving force in the development of colon cancer.

Interests: Structural Biology of Cell Signaling and Cancer Publications: View publications in PubMed Lab: http://red.dfci.harvard.edu/

LEIGH ELLIS, PhD Assistant Professor of Pathology, Dana-Farber Cancer Institute

Biography Dr. Ellis conducted his PhD studies at the Peter MacCallum Cancer Centre in Melbourne Australia through the Australian National University with Dr. Ricky Johnstone. The focus of his PhD work was investigating the apoptotic mechanisms and clinical efficacy of histone deacetylase (HDAC) inhibitors. Dr. Ellis joined the lab of Dr. Roberto Pili to carry out his postdoctoral studies in 2008 at Johns Hopkins before moving to Roswell Park Cancer Institute in 2009, where he was the recipient of a Department of Defense postdoctoral fellowship. Dr. Ellis joined Dana-Farber in 2017.

Research Dr. Ellis’ primary studies involve the investigation of novel targeted therapy combinations for the treatment of advanced genitourinary malignancies. Dr. Ellis is a former Prostate Cancer Foundation Young Investigator. Using mouse model and genomic approaches, his independent research focuses on 4 major themes involving cancer. 1) Epigenetic mediated dedifferentiation in prostate cancer initiation; 2) Insertional mutagenesis mouse models to discover genes underlying drivers of aggressive prostate cancer, 3) Genetic/Epigenetic drivers of neuroendocrine prostate cancer, and 4) Preclinical testing of targeted therapy approaches to treat aggressive prostate cancer. These studies were established by Dr. Ellis in the lab of Dr. Roberto Pili at Johns Hopkins, and is now being continued at Dana-Farber Cancer Institute, in Dr. Ellis’ newly established lab. The Ellis laboratory interests include the characterization of comprehensive molecular signatures, survival pathways and associated rational therapeutic targets in metastatic castrate resistant prostate cancers, with a specific focus on epigenetics and lineage plasticity, and their role in disease progression and therapeutic resistance. Interests: Advanced Genitourinary Malignancies, Prostate Cancer, Genomics, Epigenetics Publications: View publications in PubMed

ERIC FISCHER, PhD Assistant Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School Independent Investigator, Cancer Biology, Dana Farber Cancer Institute

Biography Dr. Fischer received his B.Sc. in molecular biology and M.Sc. in structural biology from the University of Basel and his Ph.D. in structural biology from the Friedrich Miescher Institute in Switzerland. Dr. Fischer has been recognized for his pioneering work on the structure of cereblon and the mechanism of action of thalidomide. Research The Ubiquitin Proteasome System (UPS) is involved in virtually any cellular process and frequently implicated in human pathologies. Ubiquitin, through the action of a three-enzyme cascade (E1, E2 and E3), becomes attached to substrate proteins. The posttranslational

modification with ubiquitin can serve a multitude of functions depending on the type and length of the ubiquitin chain attached to the substrate, including the control of protein abundance via proteasomal degradation. The human genome encodes for more than 600 E3 ligases, which confer specificity in the ubiquitin signaling cascade. While the process of ubiquitin transfer is well understood, the biological function and molecular mechanisms of the majority of ubiquitin ligases remain obscure. Dr. Fischer’s laboratory combines structural biology, cell biology and biochemical reconstitutions to address the molecular workings of these multi-component ubiquitin ligases. In particular, Dr. Fischer and his colleagues are interested in protein complexes and pathways that contribute to the control of gene expression and are frequently associated with human disease and cancer. Intimate understanding of the structure allows them to dissect the complex mechanisms that underlie function and regulation of such molecules and to probe their biology in a cellular context. They seek to leverage their molecular understanding to propose and test new avenues of therapeutic intervention. They are also interested in small molecules targeting the UPS such as the anti-cancer therapeutics thalidomide and derivatives. As before, they utilize a broad toolset of structural biology, proteomics, cell biology and biochemical reconstitutions to elucidate their activities and precise mode of action. Mechanistic understanding of small molecule mediated protein degradation enables the more rational design of these novel therapeutic modalities. Interests: The Ubiquitin Proteasome System (UPS), Molecular mechanisms Publications: View publications in PubMed Lab: http://fischerlab.dana-farber.org/

DAVID A. FRANK, MD, PhD Associate Professor of Medicine, Harvard Medical School Associate Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute Senior Physician

Biography Dr. Ellis conducted his PhD studies at the Peter MacCallum Cancer Centre in Melbourne Australia through the Australian National University with Dr. Ricky Johnstone. The focus of his PhD work was investigating the apoptotic mechanisms and clinical efficacy of histone deacetylase (HDAC) inhibitors. Dr. Ellis joined the lab of Dr. Roberto Pili to carry out his postdoctoral studies in 2008 at Johns Hopkins before moving to Roswell Park Cancer Institute in 2009, where he was the recipient of a Department of Defense postdoctoral fellowship. Dr. Ellis joined Dana-Farber in 2017.

Research Dr. Frank focuses on the intracellular signaling events that control the growth and differentiation of normal and malignant cells. Extracellular stimuli lead to a cascade of events that culminates in the regulation of gene expression. It is the activation or repression of specific genes that then determines cellular function. Dr. Frank and his colleagues study how these signaling events occur normally by examining the activation of kinase cascades, transcriptional networks, and key target genes. Among the mediators they have focused on are STAT transcription factors, which can be modulated by both tyrosine and serine phosphorylation, and thus may serve as a convergence point for multiple signaling pathways. Thus, one of the areas of focus in their group is how STATs, alone and in conjunction with other transcription factors, modulate gene expression throughout the genome. Dr. Frank and his team are developing targeted molecular inhibitors of STATs and other transcription factors using both rational design and chemical-biology approaches. These reagents are useful tools for dissecting the roles of signaling pathways in the growth and differentiation of normal cells. Furthermore, given the inappropriate activation of signaling pathways in malignant cells, these approaches may be useful in developing novel therapeutic strategies for the treatment of cancer. They have initiated a clinical trial of a STAT3 inhibitor identified in the lab for patients with cancer, and are analyzing the effects of this approach on the gene expression and biology of cancer cells obtained from patients on study. They are in the process of initiating clinical trials with additional transcriptional modulators identified by their group. Interests: Leukemia, Targeting Signaling Pathways for Cancer Therapy Publications: View publications in PubMed

GORDON J. FREEMAN, PhD Professor of Medicine, Harvard Medical School

Biography Dr. Freeman earned his BA in Biochemistry and Molecular Biology, and PhD in Microbiology and Molecular Genetics from Harvard University in 1979 and joined DFCI that year. He did postdoctoral training in the laboratory of Dr. Harvey Cantor and then with Dr. Lee Nadler. Research The Freeman Laboratory studies the major pathways that control the immune response by inhibiting T cell activation (PD-1/PD-L1 and B7-2/CTLA-4) or stimulating T cell activation (B7-2/CD28).

Following the discovery of PD-L1 and PD-L2 as the ligands for the PD-1 receptor on T cells, Dr. Freeman demonstrated the inhibitory function of PD-L1 and PD-L2 on T cells and showed that blockade of this pathway enhanced T cell activation, proliferation, and cytokine production. Further studies showed that PD-L1 is highly expressed by many solid tumors/hematological malignancies, and that blockade of PD-L1 enhances killing of PD-L1 positive targets by CD8 T cells. Recently, PD-1 and PD-L1 blocking antibodies were approved by the FDA for the treatment of a wide range of cancers. He received the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology for this work that led to development of PD-1 pathway blockade for cancer immunotherapy. Interests: co-stimulatory and co-inhibitory pathways, cancer immunotherapy, PD-1, PD-L1 Publications: View publications in PubMed

IRENE M. GHOBRIAL, MD Director, Michele & Steven Kirsch Laboratory Senior Physician Associate Professor of Medicine, Harvard Medical School

Biography Dr. Ghobrial received her MD in 1995 from Cairo University School of Medicine, Egypt. She completed her Internal Medicine training at Wayne State University, Mich., and her Hematology/Oncology subspecialty training at Mayo Clinic College of Medicine, Minn. She joined Dana-Farber in the field of Waldenstrom's macroglobulinemia and multiple myeloma in 2005. Research Dr. Ghobrial is a physician scientist who specializes in the field of Multiple Myeloma (MM) and Waldenström Macroglobulinemia (WM), specifically in the precursor conditions of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering disease. She

focuses particularly on the role of the malignant bone marrow niche in disease progression from early precursor conditions like MGUS/smoldering MM to overt MM. Dr. Ghobrial and her lab use MM as a model of bone metastasis and dissemination, and examine how MM can use a process of cell dissemination that is similar to cell trafficking of hematopoietic stem cell (HSCs) and cell metastasis in solid epithelial carcinomas. In addition, her laboratory research data has been rapidly translated to innovative investigator-initiated clinical trials. They have conducted over 10 phase I and II clinical trials. Their studies on MM cell trafficking have been translated to the first chemosensitization trials in patients with Multiple Myeloma. Dr. Ghobrial is the co-leader of the first consortium of clinical trials for blood cancers in collaboration with the Leukemia and Lymphoma Society to form the Blood Cancer Research Partnership (BCRP), a consortium for innovative clinical trials of 11 community oncology sites coordinated by Dana-Farber Cancer Institute. Interests: Waldenström's macroglobulinemia, Multiple myeloma Publications: View publications in PubMed Lab: http://ghobriallab.dana-farber.org/

MICHAEL GOLDBERG, PhD Assistant Professor of Microbiology & Immunobiology, Harvard Medical School

Biography Dr. Goldberg received his PhD in 2008 from MIT, where he worked in the laboratory of professor Robert Langer. He subsequently pursued post-doctoral training under the supervision of professor Philip Sharp at MIT. In 2012, he became assistant professor of Microbiology and Immunobiology at Harvard Medical School and in the Department of Cancer Immunology at Dana-Farber Cancer Institute, where he works on the development and delivery of novel therapeutics. Research The Goldberg Lab seeks to leverage the tools of drug delivery to manipulate the cell-extrinsic aspects of cancer in the tumor microenvironment. In particular, Dr. Goldberg recently joined DFCI to

apply RNAi-based therapeutics to cancer immunotherapy. He has particular expertise in the development and delivery of cancer-specific siRNAs that target synthetic lethality and aberrant alternative splicing programs. Dr. Goldberg is credited with delivering the first single-agent synthetic lethal siRNA therapeutic in vivo – siRNA targeting Parp1 – for treatment of BRCA1-deficient ovarian cancer; more recently, he demonstrated that siRNA sequences specific to the cancer-expressed M2 isoform of pyruvate kinase induce apoptosis and tumor regression – independent of the cancer type or underlying genetic lesions – without affecting the viability of normal cells. The focus of current studies includes targeting siRNA delivery to immune cells in vivo. Dr. Goldberg’s diverse training in chemistry, materials science, biotechnology, and molecular biology is combined with cutting-edge mRNA- and siRNA-based as well as nanoparticle-based therapeutic strategies, promising to yield innovative approaches to cancer immunotherapy. Interests: Development and Delivery of Novel Therapeutics to Address Cancer Publications: View publications in PubMed

TODD R. GOLUB, MD Professor, Pediatrics, Harvard Medical School Associate Professor of Pediatrics, Pediatric Oncology, Dana-Farber Cancer Institute Director, Cancer Program, Broad Institute of MIT and Harvard Howard Hughes Medical Institute Investigator

Biography Dr. Golub received his MD in 1989 from the University of Chicago. After completing subspecialty clinical and research training at Harvard Medical School, he joined DFCI, where he is the Charles A. Dana Investigator in Human Cancer Genetics. In 2002, he was appointed investigator of the Howard Hughes Medical Institute in recognition of his work in cancer genomics. He was recently named founding Director of the Cancer Program of the Broad Institute of Harvard and MIT focusing on genomic medicine. Research Dr. Golub’s laboratory focuses on the use of genomic and computational methods to study biological and clinical questions in

cancer. Particular emphasis is placed on the use of genomics methods for the discovery of clinically significant diagnostic and prognostic biomarkers and potential new therapeutic targets. Methods to incorporate genomic approaches into the drug discovery process are also being developed. Interests: Cancer genome, precision medicine Publications: View publications in PubMed

NATHANAEL S. GRAY, PhD Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School Professor, Cancer Biology, Dana-Farber Cancer Institute

Biography Dr. Gray received his PhD in chemistry from the University of California at Berkeley in 1999. He then moved to the Genomics Institute of the Novartis Research Foundation in San Diego, where after serving as a staff scientist and group leader of kinase inhibitor chemistry, he was named director of biological chemistry in 2001. Dr. Gray recently joined the faculty of Harvard Medical School and DFCI to continue his research using synthetic chemistry and functional small molecule discovery to modulate biological pathways important in cancer.

Research Synthetic Chemistry/Functional Small Molecule Dr. Gray’s research focuses on using synthetic chemistry and functional small molecule discovery to modulate biological pathways important in cancer. The Gray laboratory at DFCI has extensive experience in the lead optimization of small molecule inhibitors to achieve agents with the requisite potency, selectivity, pharmacological properties and safety profile for clinical development. His research group has been responsible for the discovery of novel inhibitors of wild-type and mutant forms of EGFR (WZ4002), mTor (Torin1 and Torin 2), Bcr-Abl (GNF-2, GNF-5, HG-7-85-01), Mps1 (Mps1-IN-1 Mps1-IN-2), Erk5 (XMD8-92), b-Raf, LRRK2 (LRRK2-IN-1), Jnk1,2,3 (JNK-IN-7) and Ephrin kinases which have become widely used research tools and have inspired several drug discovery programs. Interests: kinase inhibitors, small molecule discovery, combinatorial gene-family targeted libraries Publications: View publications in PubMed

Lab: http://graylab.dfci.harvard.edu/

JAMES D. GRIFFIN, MD Chair, Medical Oncology Senior Physician Professor of Medicine, Harvard Medical School

Biography Dr. Griffin received his MD from Harvard Medical School in 1974. After residency training in internal medicine at Johns Hopkins Hospital, he completed a hematology fellowship at Massachusetts General Hospital and a medical oncology fellowship at DFCI. In 1981, he joined the staff of DFCI, where he is now director of the Leukemia Program and chair of the Department of Medical Oncology. He also serves on the scientific advisory boards of the Lombardi Cancer Center at Georgetown University and the Johns Hopkins Cancer Center. Research Dr. Griffin's laboratory is focused on understanding the genetic events that cause leukemia. The major laboratory interests can be divided into

three broad areas: 1. Mechanisms of transformation by the BCR/ABL oncogene. The product of the BCR/ABL oncogene is an activated tyrosine kinase which induces a myeloproliferative syndrome in humans and mice. p210BCR/ABL transforms hematopoietic cells at least in part by constitutively activating signal transduction pathways which are normally tightly regulated by growth factors such as IL-3 or GM-CSF, such as those involved in blocking apoptosis. Several critical targets of BCR/ABL have been identified, including CRKL, SHP2, PI3K, SHIP, and RAS. Defining the individual contribution of each pathway to CML is underway, as are gene discovery approaches to identifying novel targets. 2. Mechanisms of transformation by the FLT3 oncogene and development of targeted therapies against FLT3. FLT3 is mutated in about 35% of all cases of AML. The lab has developed a small molecule tyrosine kinase inhibitor that blocks signaling from FLT3, which is currently being tested in clinical trials. In vitro studies of mechanism and murine models are being used to develop the next generation of AML therapies using this inhibitor as part of the therapy. 3. Signaling of the Notch receptor in hematopoietic and epithelial cells. Dr. Griffin’s lab has recently cloned several members of the Notch signaling pathway, a family of transcriptional regulators (mastermind-like genes) that modulates expression of Notch-regulated genes in a variety of cell lineages. One family member, MAML2, has recently been shown to be mutated in mucoepidermoid cancer and appears to be the cause of that neoplasm. Interests: Leukemia, Myelodysplasia Publications: View publications in PubMed

WILLIAM C. HAHN, MD, PhD Chief Research Strategy Officer (CRSO), Dana-Farber Cancer Institute Chair, Executive Committee for Research Deputy Chief Scientific Officer Chief, Division of Molecular and Cellular Oncology Director, Center for Cancer Genome Discovery Physician Professor of Medicine, Harvard Medical School Institute Member, Broad Institute of Harvard & MIT

Biography Dr. Hahn received his MD and PhD from Harvard Medical School in 1994. He then completed clinical training in internal medicine at Massachusetts General Hospital and medical oncology at DFCI. He conducted his postdoctoral studies with Dr. Robert Weinberg at the Whitehead Institute and joined the faculty of DFCI and Harvard Medical School in 2001. Research The Hahn laboratory has developed systematic approaches to discover and characterize genes that drive cancer initiation, progression and tumor maintenance. Our overarching goal is to understand how

mutations cooperate to drive cancer initiation and progression, both to decipher the biological basis of cancer and to develop new therapeutic approaches. The Hahn laboratory uses systematic approaches to:

1) Decipher the molecular pathways that underlie cellular transformation 2) Discover cancer-specific genetic vulnerabilities 3) Identify genetic alterations that promote therapeutic resistance

Interests: Functional genomics and human cell transformation, precision cancer medicine Publications: View publications in PubMed Lab: http://hahnlab.dana-farber.org/

W. NICHOLAS HAINING, BM, BCh Adjunct, Department of Immunology and Virology Assistant Professor, Pediatric Oncology Associate Professor of Pediatrics, Harvard Medical School Associate Member, Broad Institute of MIT and Harvard

Biography Dr. Haining trained as a pediatric oncologist at the Dana Farber Cancer Institute and Children's Hospital Boston before doing a post-doc in Lee Nadler's laboratory at Dana Farber Cancer Institute. He started his own lab at DFCI in 2008, and still sees patients in the Jimmy Fund Clinic and at Children's Hospital. Research The Haining lab studies the mechanisms that regulate T cell function in humans. Dr. Haining uses a range of approaches including cellular immunology, functional genomics, epigenetics, and single cell profiling to understand why protective T cell memory fails to occur in cancer and

chronic viral infection. Some of the ongoing projects in the Haining lab include:

1) Single cell analysis of functional and exhausted T cells in tumors and chronic viral infections from humans and mouse models.

2) Transcriptional regulation of T cell exhaustion. 3) Genome editing of T cells. 4) Immunotherapy target discovery.

Interests: Single cell analysis, immunotherapy target discovery, T cell Publications: View publications in PubMed Lab: http://haining.dfci.harvard.edu/research/

F. STEPHEN HODI JR., MD Director, Melanoma Center Director, Center for Immuno-Oncology Institute Physician Professor of Medicine, Harvard Medical School

Biography Dr. Hodi received his MD degree from Cornell University Medical College in 1992. Dr. Hodi competed his postdoctoral training in Internal Medicine at the Hospital of the University of Pennsylvania, and Medical Oncology training at Dana-Farber cancer Institute where he joined the faculty in 1995. Research Dr. Hodi’s research in malignant melanoma focuses on gene therapy, the development of immune therapies, and first-into-human studies. Dr. Hodi was the first to report the clinical use of CTLA-4 blocking antibodies in patients. The work included defining mechanisms of action

of CTLA-4 blockade and led to the seminal study that revealed for the first time a survival advantage for patients and the basis for FDA approval. In addition, Dr. Hodi demonstrated the first successful use of a tyrosine-kinase inhibitor against KIT in melanoma, confirming the principle that melanoma may be treated based on the mutational status of patient’s tumor. Interests: Cancer immunology, combination immunotherapies, Melanoma, gene therapy Publications: View publications in PubMed

PASI A. JÄNNE, MD, PhD Director, Lowe Center for Thoracic Oncology Scientific Director, Belfer Institute for Applied Cancer Science Senior Physician Professor of Medicine, Harvard Medical School

Biography Dr. Jänne received his MD and PhD from the University of Pennsylvania in 1996. He completed postgraduate training in internal medicine at Brigham and Women's Hospital and in medical oncology at DFCI in 2001. He is the director of the Lowe Center for Thoracic Oncology and the Scientific Director of the Belfer Center for Applied Cancer Science. Research His main research interests include studying the therapeutic relevance of oncogenic alterations in lung cancer. He was one of the co-discoverers of epidermal growth factor receptor (EGFR) mutations and has led the development of therapeutic strategies for patients

with EGFR mutant lung cancer. Current areas of focus in the lab include: 1. Identification and study of mechanisms of acquired drug resistance to targeted therapies 2. Development of novel combination therapies to overcome and/or prevent the emergence of drug resistance 3. Identification & validation of novel targeted therapies & therapeutic combinations for lung cancer 4. Genomic analyses of never-smokers with lung cancer 5. Generation and study of patient-derived in vitro and in vivo tumor models

These pre-clinical studies are complemented by clinical trials for lung cancer patients at the Lowe Center for Thoracic Oncology at DFCI.

Interests: Targeted therapy, Lung Cancer, Cancer Immunology, genetic profiling of non-small cell lung cancer, novel combination therapies to overcome drug resistance Publications: View publications in PubMed Lab: http://jannelab.dfci.harvard.edu/index.html

BRUCE E. JOHNSON, MD Chief Clinical Research Officer Institute Physician Professor of Medicine, Harvard Medical School

Biography Dr. Johnson received his MD from the University of Minnesota in 1979 and his postgraduate training at the University of Chicago and the National Cancer Institute. After serving at NCI, where he most recently headed the Lung Cancer Biology Section, he joined DFCI in 1999. He currently leads the Dana-Farber/Harvard Cancer Center Lung Cancer Program and is the Chief Clinical Research Officer at the Dana-Farber Cancer Institute. Research Dr. Johnson’s translational research is devoted to testing novel therapeutic agents for their efficacy against lung cancer and other

thoracic malignancies with specific genomic changes. The Johnson Laboratory identified the link between mutations of the epidermal growth factor receptor (EGFR) and response to the EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. Subsequent research has changed the paradigm of diagnosis and treatment for patients with non-small cell lung cancer and sensitizing EGFR mutations. The systematic characterization of the genomic changes in lung cancer has identified multiple changes that can lead to treatment with approved targeted agents (gefitinib and erlotinib) or enrollment onto ongoing investigation studies. These include EGFR, KRAS, HER2, BRAF, and PIK3CA mutations as well as the ALK and ROS1 rearrangements. Dr. Johnson’s research team carries out systematic genomic characterization of nearly all of our advanced non-small cell lung cancer patients for EGFR, KRAS, HER2, BRAF, PI3KA mutations, ALK and ROS1 rearrangements, plus HER2 and MET amplification. Interests: Non-small cell lung cancer, Small cell lung cancer, Genomic characterization, Mesothelioma Publications: View publications in PubMed

CIGALL KADOCH, PhD Assistant Professor, Pediatrics, Harvard Medical School Assistant Professor, Pediatric Oncology, Dana-Farber Cancer Institute Principal Investigator, Pediatric Oncology, Dana-Farber Cancer Institute Institute Member, Chemical Biology, Broad Institute of MIT and Harvard

Biography Dr. Kadoch earned her B.A. in Molecular and Cellular Biology from the University of California Berkeley in 2007. She obtained her PhD in Cancer Biology from Stanford University School of Medicine in 2012. As a post-doctoral scholar at Stanford Medical School, Dr. Kadoch helped identify a group of proteins that appear to play a significant role in the suppression of many types of cancer. She was an undergraduate when she received the AACR Thomas J. Bardos Science Education Award for Undergraduate Students, then a graduate student when she won the WICR Scholar Award in 2010. Today she is a newly-independent scientist at Dana-Farber Cancer Institute.

Research Dr. Kadoch’s laboratory investigates how disruption of a protein complex that governs DNA architecture and gene expression can lead to cancer. By controlling whether regions of the genome are completely compact or relatively accessible, groups of proteins called chromatin-remodeling complexes regulate gene activity-- including the activity of genes that can promote cancer. They have discovered that mutations in the genes encoding the protein subunits of one such chromatin-remodeling complex, the BAF complex, occur in more than one-fifth of all human cancers. As a graduate student, Dr. Kadoch discovered the underlying mechanism of a rare but aggressive cancer called synovial sarcoma, for which BAF complex perturbation is the driving oncogenic event in 100% of cases. This has provided a strong foundation upon which to interrogate the mechanistic basis for BAF complex compromise in human cancer. Combining biochemistry, structural and molecular biology, functional genomics and now chemistry, Kadoch’s lab team studies how this protein complex is pieced together in cells and aims to identify molecules that can restore proper assembly and function in cancer cells with BAF complex mutations. These results may potentially yield a new class of cancer therapeutics. Interests: Genomics, BAF complexes, Biochemistry, Chromatin regulation Publications: View publications in PubMed Lab: http://www.kadochlab.org/

WILLIAM G. KAELIN JR., MD Professor of Medicine, Harvard Medical School Investigator, Howard Hughes Medical Institute

Biography Dr. Kaelin received his MD from Duke University in 1982 and was a house officer and chief resident in internal medicine at Johns Hopkins Hospital. He was a medical oncology clinical fellow at Dana-Farber and a postdoctoral fellow in the laboratory of Dr. David Livingston, where he began his studies of tumor suppressor proteins. He became an independent investigator at Dana-Farber in 1992, and a Howard Hughes Medical Institute Investigator and Professor of Medicine at Harvard Medical School in 2002. Research A Howard Hughes Medical Investigator since 1998, Dr. Kaelin's research seeks to understand how, mechanistically, mutations

affecting tumor-suppressor genes cause cancer. His long-term goal is to lay the foundation for new anticancer therapies based on the biochemical functions of tumor suppressor proteins. His work on the VHL protein helped to motivate the eventual successful clinical testing of VEGF inhibitors for the treatment of kidney cancer. Moreover, this line of investigation led to new insights into how cells sense and respond to changes in oxygen, and thus has implications for diseases beyond cancer, such as anemia, myocardial infarction and stroke. Dr. Kaelin’s laboratory studies the functions of the proteins encoded by specific tumor-suppressor genes. The lab’s long-term goal is to help develop new anticancer therapies. For example, it might be possible to develop a drug that would mimic the behavior of a particular tumor-suppressor protein (for example, by inactivating a specific enzyme involved in cell growth). It might also be possible to design strategies for killing only those cells in which a particular tumor-suppressor protein has been inactivated (thus sparing normal cells). Interests: Functions of Tumor Suppressor Proteins Publications: View publications in PubMed Lab: http://kaelin.dfci.harvard.edu/Kaelin_Lab_website/Home_page_kaelin_lab.html

JUSTIN KIM, PhD Assistant Professor, Dana-Farber Cancer Institute Assistant Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

Biography Dr. Kim earned his Bachelor’s degree in Chemistry and Physics and his Master’s degree in Chemistry in 2007, both from Harvard University. In 2013, Dr. Kim earned his PhD in Organic Chemistry from Massachusetts Institute of Technology. He completed his postdoctoral fellowship at the Miller Institute at UC Berkeley, and went on to complete his postdoctoral research fellowship at Stanford University in 2016. Research Research in Dr. Kim’s lab takes a bottom-up approach to tackling molecular challenges in cancer biology. Basic chemical research – development of new reactions, exploration of novel synthetic

strategies, discovery of new molecular reactivity, and synthesis of complex molecular architectures – fuels their drive to access useful compounds for the study and manipulation of biological systems. The Kim Lab’s biological interests lie in the areas of tumor hypoxia, gram-negative pathogens, and protein-protein interactions. Exploiting functional specificity: Drug discovery efforts predominantly target human pathologies by exploiting the structural complementarity between small molecules and the binding pockets of dysregulated proteins. Dr. Kim and his colleagues envision the design of new therapeutic and imaging agents that are responsive to the unique chemical microenvironments of diseased cells and pathogens. Such a strategy, enabled by fundamental chemical developments and access to new compositions of matter, will facilitate both the discovery of new pharmaceutical agents and the repurposing of old drugs for new diseases. Probing macromolecular interactions: Dr. Kim’s lab will take a chemical approach to targeting macromolecular interactions. While much of life’s processes is governed by protein-protein and protein-nucleic acid interactions, only a small fraction of these can be manipulated using small molecules. The identification of small organic molecules capable of binding flat interfacial surfaces is incredibly difficult, but they envision that the development of a high throughput discovery platform employing a set of privileged molecular scaffolds will enable them to target some of these traditionally undruggable targets. Interests: Chemistry, Chemical Biology Publications: View publications Lab: http://kimlab.dana-farber.org/

PHILIP J. KRANZUSCH, PhD Assistant Professor of Microbiology and Immunobiology, Dana-Farber Cancer Institute Member of the Faculty, Harvard Medical School

Biography Dr. Kranzusch received his B.S in Molecular Biology from the University of Wisconsin-Madison and his Ph.D. in Virology from the Harvard University. He completed his postdoctoral training in Dr. Jennifer Doudna and Dr. James Berger’s Laboratory. Research The Kranzusch lab is working to understand how cells respond to pathogens, and how these signaling pathways can be harnessed for new potential therapies to treat cancer and autoimmune diseases. Importantly, many critical aspects of the cellular response to infection remain unknown. The Kranzusch lab uses an approach to reconstitute signaling outside of the cell using highly purified components in order to

understand the mechanistic and structural underpinnings that control human immunity. Interests: Signaling pathway, tumor immunity, pathogen recognition Publications: View publications in PubMed Lab: http://kranzuschlab.med.harvard.edu/default.html

DONALD W. KUFE, MD Distinguished Physician, Dana-Farber Cancer Institute Professor of Medicine, Harvard Medical School

Biography Dr. Kufe received his MD in 1970 from the University of Rochester School of Medicine. After a clinical fellowship in medical oncology at Dana-Farber Cancer Institute, he joined the staff in 1979. He has served as chief of the Division of Cancer Pharmacology, deputy director of the Dana-Farber Cancer Center, director of the Harvard Phase I Oncology Group and leader of the Experimental Therapeutics Program. He is an editor of the textbook "Cancer Medicine." Research Basic research in the Kufe laboratory is focused on the role of the MUC1 protein in oncogenesis. Translational research efforts are

directed toward the development of agents that target the MUC1 transforming function. The Kufe laboratory identified the human DF3/MUC1 carcinoma-associated protein in the early 1980s. Initial studies demonstrated that MUC1 is aberrantly overexpressed in >90% of human breast cancers. Subsequent work by multiple laboratories showed that MUC1 is expressed at elevated levels by diverse carcinomas and certain hematologic malignancies. Estimates indicate that MUC1 is overexpressed in about 900,000 of the 1.4 million tumors diagnosed each year in the United States. Translational research in the Kufe laboratory has resulted in the development of a recombinant vaccinia virus expressing MUC1 that has completed Phase I trials and is under evaluation in Phase II studies for the treatment of MUC1-positive tumors. Another vaccine developed in the Kufe laboratory involves the fusion of MUC1-positive cancer cells with dendritic cells. Phase II trials of the fusion cell vaccine are underway in for patients with breast cancer, renal cancer, ovarian cancer and multiple myeloma. A Phase III trial of Ad.Egr-TNF for pancreatic cancer is also underway as another approach for inducing immunity against MUC1. Translational work is also underway to block MUC1-C subunit function with soluble receptors and antibodies against the MUC1-C extracellular domain. The demonstration that MUC1-C transforming function is dependent on the formation of oligomers has also provided the experimental framework for developing peptides and small molecules that block its oligomerization. Interests: Translational Pharmacology, Early Therapeutic Trials Publications: View publications in PubMed

ANDREW A. LANE, MD, PhD Physician Assistant Professor of Medicine, Harvard Medical School

Biography Dr. Lane received his MD and PhD degrees from Washington University. He completed his residency in internal medicine at Brigham and Women's Hospital, and his fellowships in hematology and medical oncology at Dana Farber Cancer Institute. His research focuses on developing new treatments for leukemia by studying the genetic changes that occur in cancer and how they alter the normal development of blood cells. Research The Lane lab strives to expose and target the abnormal biology that drives blood cancers, particularly those with poor prognoses or without specific treatments. Dr. Lane and his team focus

predominantly on acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and blastic plasmacytoid dendritic cell neoplasm (BPDCN), and the disruption of normal stem cell development in these hematologic malignancies. Their goal is to understand the genetic and epigenetic changes that alter gene regulation in malignant hematopoietic cells, develop innovative model systems to study those abnormalities, and ultimately discover novel therapeutic strategies. They are particularly focused on studying aberrant signaling or altered chromatin dynamics in leukemia, including changes in nucleosome binding proteins, histone modifying enzymes, and histones themselves. Lane and his team hope that their research leads to better tolerated therapies and more cures for patients with leukemia and other blood disorders. Interests: Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), Stem cell transplantation Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/lanelab/

ANTHONY G. LETAI, MD, PhD Physician Associate Professor of Medicine, Harvard Medical School

Biography Dr. Letai received his MD and PhD at the University of Chicago. His PhD was done under the supervision of Elaine Fuchs. Dr. Letai then completed clinical training in Internal Medicine at Brigham and Women's Hospital, Boston. Following this, he walked across the street to do a fellowship in Hematology and Oncology at Dana-Farber Cancer Institute. He was introduced to apoptosis and BCL-2 family proteins as a post-doctoral researcher in the laboratory of the late Stanley Korsmeyer. In 2004, Dr. Letai became independent investigator at Harvard Medical School and Dana-Farber Cancer Institute where he is now an Associate Professor in Medicine.

Research Research in the Letai lab centers on understanding how cells decide to make the commitment to apoptosis. The Letai Lab focuses on the role of BCL-2 family proteins, as these proteins play the key roles in deciding whether cells should commit to apoptosis, and in executing the mitochondrial permeabilization that is the required hallmark of mitochondrial apoptosis. Dr. Letai’s lab proposed the concept that BH3-only proteins can play two different roles: activators, which can directly activate BAX and BAK; and sensitizers, which antagonize antiapoptotic proteins like BCL-2 and MCL-1. Dr. Letai’s lab is also studying how some cells can be "primed for death" by possessing large amounts of activator BH3-only proteins sequestered by anti-apoptotic proteins. They can detect such cells by means of a technique we developed called BH3 profiling. Surprisingly little is known about the details of death signaling due to chemotherapy. Dr. Letai’s lab has recently found BH3 profiling can measure priming in primary cancer tissues and normal tissues, and are comparing priming results with actual clinical response. An important aim of the Letai lab is to apply what they learn to the improved therapy of human cancers. While Dr. Letai’s interests thus far have focused on leukemia and lymphoma, it is clear the apoptosis plays an important role in the killing of nearly all cancers. Thus, the Letai lab looks forward to applying their strategies to other cancers, and have begun studies in ovarian, lung, and breast cancers. Interests: Leukemia Publications: View publications in PubMed Lab: http://letailab.dana-farber.org/

X. SHIRLEY LIU, PhD Director, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute Professor of Biostatistics and Computational Biology, Harvard T.H. Chan School of Public Health

Biography Dr. X. Shirley Liu graduated summa cum laude from Smith College double majoring in Biochemistry and Computer Science in 1997, and received PhD in Biomedical Informatics and PhD minor in Computer Science from Stanford University in 2002. She is now Professor at the Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute and Harvard School of Public Health. She is the Director of the Center of Functional Cancer Epigenetics at Dana-Farber Cancer Institute, and an associate member of the Broad Institute. Her research focuses on computational cancer epigenetics, and developing algorithms to model the specificity and function of transcription factors, chromatin regulators and lncRNAs in tumor development,

progression, drug response and resistance. Research Dr. Liu is a computational biologist with expertise in cancer epigenetics. Her research focus is integrating data from ChIP-seq, RIP-seq, DNase-seq, MNase-seq, RNA-seq, and other high throughput genomics data to model the specificity and function of transcription factors, chromatin regulators and lncRNAs in tumor development, progression, drug response and resistance. The Liu Laboratory research focuses on algorithm development and integrative mining from high throughput data to understand gene regulation in cancer biology. Her laboratory developed a number of widely used algorithms for transcription factor motif finding, ChIP-chip/seq and DNase-seq data analysis. In epigenetics, she and colleagues generated the first high throughput nucleosome map in the human genome and were the first to use the dynamics of nucleosome and DNase hypersensitivity to predict driving transcription factors and their genome-wide binding in a biological process. In cancer biology, she and colleagues identified the function of estrogen receptor, androgen receptor, and FoxA1 in breast and prostate cancers, found the direct targets of NOTCH1 in T-LL, and reported the switch of EZH2 from a transcriptional repressor as part of the PRC2 to a transcriptional co-activator in hormone independent prostate cancers. Interests: Computational Cancer Epigenetics, CRISPR library design, Synthetic Lethality Publications: View publications in PubMed Lab: http://liulab.dfci.harvard.edu/

DAVID M. LIVINGSTON, MD Emil Frei Professor of Genetics and Medicine, Harvard Medical School Chairman, Executive Committee for Research, Dana-Farber Cancer Institute

Biography Dr. Livingston received an A.B. cum laude from Harvard College in 1961, an M.D., magna cum laude, from Tufts University School of Medicine in 1965, and served his internship and residency in internal medicine at the Peter Bent Brigham Hospital in Boston (now Brigham and Women's Hospital). In 1967, he became a Research Associate at the National Cancer Institute (NCI) in molecular biology and biochemistry; he continued his work as a Research Fellow in Biological Chemistry at Harvard Medical School in 1969. Dr. Livingston returned to NCI in 1971 as a Senior Staff Fellow where he began his career in cancer research. He was recruited to Dana-Farber (then the Children’s Cancer Research Foundation) in 1973.

Research Dr. Livingston’s research program is aimed at understanding the functional properties of four sets of nuclear proteins, each of which plays a major role in the suppression by human cells of certain transformed/neoplastic characteristics. They are the pocket protein family (pRB, p107, p130); p300 and CBP; p400 and TRRAP; and BRCA1 and BRCA2. Analysis of the functions of BRCA1 and BRCA2 as breast/ovarian cancer-suppressing elements serve as a link to the Breast Cancer Program, and the work on the other three sets of transformation-suppressing proteins underlie Dr. Livingston’s group’s participation in the Cancer Cell Biology Program. Furthermore, the laboratory contributes to an ongoing nodal point interaction between these two Programs. Dr. Livingston is also working on converting elements of recent discovery of p300/CBP function into new screens for small molecule agents that interfere with hypoxia-driven tumor survival/proliferation responses. Interests: Molecular Pathogenesis of Breast and Ovarian Cancer Publications: View publications in PubMed

A. THOMAS LOOK, MD Professor of Pediatrics, Harvard Medical School Vice-Chair for Research, Pediatric Oncology, Dana-Farber Cancer Institute

Biography Dr. Look received his MD in 1975 and residency training in pediatrics at the University of Michigan. He completed a fellowship in pediatric oncology at St. Jude Children's Research Hospital, where he trained in the molecular biology of cancer and eventually became chair of the Experimental Oncology Department. In 1999, he joined DFCI as vice chair for research in the Department of Pediatric Oncology. Research Dr. Look’s lab use zebrafish, in combination with murine and cell culture systems, to dissect developmental pathways subverted in human cancer. Zebrafish have been shown to share conserved pathways of development and disease pathogenesis with humans,

permitting the identification of novel genes that are activated (oncogenes) or inactivated (tumor suppressors) during malignant transformation. They are using transgenic strategies to generate conditional zebrafish models of leukemias and solid tumors. Dr. Look’s group is currently studying the respective contributions of novel genes to the molecular pathogenesis of myelodysplastic syndrome and acute myeloid leukemia, and applying similar approaches to study peripheral sympathetic nervous system development and to identify tumor suppressors in childhood neuroblastoma. They have also isolated a tumor-prone, mutant p53 zebrafish to study pathways involving this key regulator of DNA repair, cell cycle regulation, and apoptosis. Dr. Look’s most advanced zebrafish model involves a transgenic line that develops T cell acute lymphoblastic leukemia (T-ALL). They are using this model to conduct one of the first cancer-related vertebrate genetic modifier screens, which will allow the identification of enhancers and suppressors of T-ALL progression. Using in vitro genome-scale location analysis (GSLA), they are also identifying the direct targets of oncogenic transcription factors and validating candidate target genes utilizing short interfering RNA strategies in human T-ALL cell lines. Through the combined use of these approaches, Dr. Look hopes to uncover novel genes and targets for the development of small-molecule inhibitors as therapeutics. Interests: Genetic Models of Leukemogenesis and Neuroblastoma Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/looklab/

JULIE-AURORE LOSMAN, MD, PhD Physician Assistant Professor, Medicine, Harvard Medical School Assistant Professor, Medical Oncology, Dana-Farber Cancer Institute Associate Physician, Medicine - Hematology, Brigham and Women's Hospital

Biography Dr. Losman earned her B.A. in Biology in 1994 from Columbia College, Columbia University. She earned her MPhil in 1997 and her PhD in 2001, both in Molecular Biology from Columbia University Graduate School of Arts and Sciences. In 2003, Dr. Losman earned her MD from Columbia University College of Physicians and Surgeons. Research The goal of Dr. Losman’s laboratory is to identify vulnerabilities in leukemia cells that can be targeted therapeutically in the hopes of

developing novel strategies to treat hematologic malignancies and other cancers. One of the pathways Dr. Losman’s group studies is the hypoxia signaling pathway. EglNs (also called PHD) are oxygen-sensitive 2-oxoglutarate-dependent dioxygenases that catalyze the prolyl hydroxylation of the HIFα (hypoxia-inducible factor) subunit of the HIF heterodimer. This targets HIFα for polyubiquitylation and subsequent proteasomal degradation. Inhibition of EglN results in accumulation of HIFα and subsequent activation of hypoxia-inducible gene transcription. Dr. Losman and her colleagues have found that inhibition of EglN inhibits the proliferation of myeloid leukemia cells, suggesting that HIF functions as a myeloid tumor suppressor. This finding has motivated their efforts to determine if inhibitors of the HIF prolyl hydroxylases, which are now in clinical trials for the treatment of anemia, can have therapeutic benefit in myeloid leukemia. Another focus of Dr. Losman’s laboratory is studying the mechanisms by which Isocitrate Dehydrogenase (IDH) mutants promote cellular transformation. Wild-type IDH enzymes are metabolic enzymes that convert isocitrate to 2-oxoglutarate. Cancer-associated IDH mutants instead produce R-2-hydroxyglutarate (R-2HG), a metabolite that is normally found at very low levels in cells. R-2HG is necessary and sufficient to mediate the transforming effects of mutant IDH. They are currently working to identify the downstream targets of R-2HG that mediate transformation, and working to identify metabolic vulnerabilities that are induce by the presence of this abnormal metabolite in cells. Interests: Leukemia, Clonal myeloid diseases Publications: View publications in PubMed

WAYNE A. MARASCO, MD, PhD Professor of Medicine, Harvard Medical School

Biography Dr. Marasco received his PhD in 1980 from the University of Connecticut School of Medicine and postdoctoral training at the University of Michigan Medical School, where he also earned an MD in 1986 and completed training in internal medicine. He received his subspecialty training in infectious diseases at Harvard Medical School, and joined DFCI in 1989. In 2003, he founded the National Foundation of Cancer Research Center for Therapeutic Antibody Engineering to expand the use of human monoclonal antibodies in the treatment of cancer. In 2009, he was listed among 13 top scientists in their field as the 21st century medicine "Pioneers of Medicine Progress" by US News & World report. He is head of an accomplished research laboratory in the area of cancer and infectious disease immunotherapy.

Research Dr. Marasco’s research interests are primarily in the field of human antibody engineering and regenerative medicine. Dr. Marasco’s laboratory focuses on the engineering and use of human antibodies in discovery research and disease treatment. His lab is working in three disease areas: cancer, emerging infectious diseases, and HIV/AIDS, a breadth of investigation made possible by the development and use of state-of-the-art tools in the field of antibody engineering that support his research efforts. More recently, the Marasco Lab has been developing humanized mice to support our targeted immunotherapy studies and to investigate the roles of human adult stem cells in regenerative medicine. In an effort to greatly expand the use of human monoclonal antibodies (Mab) in the treatment of cancer, Dr. Marasco founded the National Foundation of Cancer Research (NFCR) Center for Therapeutic Antibody Engineering (CTAE). His CTAE laboratory at Dana-Farber Cancer Institute is working with cancer investigators around the globe to utilize our human antibody library to discover new human Mab for the treatment of cancer. In this way, the CTAE can facilitate a broad range of discovery and translational research in cancer that would not be possible for a single laboratory. This also allows CTAE to work with some of the most accomplished cancer investigators in the world.

Interests: Human antibody engineering, regenerative medicine

Publications: View publications in PubMed

Lab: http://www.marascolab.com/

MATTHEW L. MEYERSON, MD, PhD Professor of Pathology, Dana-Farber Cancer Institute & Harvard Medical School Institute Member, Broad Institute

Biography Dr. Meyerson received his MD in 1993 and PhD in 1994 from Harvard University. After a residency in clinical pathology at Massachusetts General Hospital and a research fellowship with Dr. Robert Weinberg at the Whitehead Institute, he joined DFCI in 1998. Dr. Meyerson serves as Professor of Pathology at Dana-Farber Cancer Institute and Harvard Medical School, as Director of the Center for Cancer Genome Discovery at DFCI (with Dr. William Hahn), and as Senior Associate Member of the Broad Institute. Research

Dr. Meyerson has concentrated on using genomic approaches to understand the biology and genetics of human lung carcinomas. More broadly, his laboratory is focused on cancer genome discovery and pathogen discovery in human. The goal of the Meyerson laboratory is to improve the treatment of human cancer and to extend the lives of cancer patients, with a particular focus on lung cancer. Research approaches include the use of cancer genomics and genome-inspired drug discovery. In addition, research interests focus on finding infectious agents that cause hitherto mysterious human diseases. Interests: Lung cancer, cancer genomics, pathogen discovery, datasets Publications: View publications in PubMed Lab: http://meyersonlab.dana-farber.org/

NIKHIL C. MUNSHI, MD Director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center Senior Physician Professor of Medicine, Harvard Medical School

Biography Dr. Munshi received his MD from Maharaja Sayjirao University, India, in 1984. He completed his postgraduate training in Internal Medicine at SSG Hospital and Maharaja Sayjirao University, followed by fellowships at Johns Hopkins Oncology Center and Indiana University Medical Center. In 2001, he joined Dana-Farber Cancer Institute and is currently the Associate Director of the Jerome Lipper Myeloma Center. Research A major focus of Dr. Munshi’s laboratory research has been identifying novel targets and antigens associated with multiple myeloma, and developing molecular therapeutic strategies including immunotherapy

and immuno-gene therapy. In an effort to define the ideal time for vaccination, Dr. Munshi and his colleagues discovered both a decreased number and decreased activity of T regulatory cells in myeloma. They identified the cytokines produced in the bone marrow microenvironment that are responsible for this T regulatory cell dysfunction, making these cytokines an important target for improving T cell homeostasis. Moreover, based on their observation of the costimulatory effects of Revlimid (lenalidomide) through the B7-CD28 pathway, Dr. Munshi and his team are also developing therapeutic strategies using this agent, to improve immune responses. Based on their in vitro results, they are developing clinical trials to evaluate vaccine strategies in myeloma. In particular, they studied the idiotype as a myeloma-specific antigen and observed specific immune responses. However, because therapeutic strategies directed against a single tumor-associated target may lead to immunological escape, they are identifying additional novel antigens with demonstrated in vivo immunogenicity in myeloma using pre- and post-vaccination patient serum and the Serological Analysis of Recombinant cDNA Expression Library (SEREX). For this work, they have cloned a series of molecules to form a panel of antigens for effective peptide- and protein-based vaccination in myeloma. The long-term goal of Dr. Munshi and his team’s research efforts is to develop novel therapeutic approaches to myeloma based on bench-side research and then to evaluate patient responses to find better avenues to effective therapy. Interests: Immunotherapy and Molecular Manipulation in Multiple Myeloma Publications: View publications in PubMed

LEE M. NADLER, MD Senior Vice President, Experimental Medicine Physician Virginia and D.K. Ludwig Professor of Medicine, Harvard Medical School

Biography Dr. Nadler received his MD from Harvard Medical School in 1973. After residency training at Columbia-Presbyterian Medical Center and training at the National Cancer Institute in tumor immunology, he completed a medical oncology fellowship at DFCI, where he joined the staff in 1980. During his tenure at DFCI, he has served as chief and chair of several departments. Research Dr. Nadler’s research efforts focus on Induction of Alloantigen-Specific Anergy for Allogeneic HSCT and Antitumor Immunity. Dr. Nadler’s laboratory focuses on translational bench-to-bedside and bedside-to-bench research. First, investigating the mechanisms of tolerance induction to improve the outcome of allogeneic stem cell

transplantation; then attempting to induce antigen-specific tumor immunity. His lab has completed two phase I studies using anti-B7 blockade to induce alloantigen-specific anergy in patients undergoing haploidentical human stem cell transplantation. They have demonstrated feasibility, less than expected incidence of GVHD, and fewer than expected infections. Going forward, their focus is on the retention of pathogen and tumor-specific immunity. Interests: Lymphoma, Bone marrow transplant, Immunotherapy Publications: View publications in PubMed

CARL NOVINA, MD, PhD Associate Professor, Dana-Farber Cancer Institute & Harvard Medical School Associate Member, Broad Institute of Harvard and MIT

Biography Dr. Novina received his M.D. from Columbia University, College of Physicians and Surgeons in 2000 and his Ph.D. from Tufts University, Sackler School of Graduate Biomedical Sciences in 1998. His graduate work in Ananda Roy’s laboratory resulted in 10 publications examining transcriptional regulation of TATA-less promoters. As a postdoctoral fellow in Phillip Sharp’s laboratory at the Massachusetts Institute of Technology, Dr. Novina studied the basic mechanisms of microRNAs, demonstrated the use of siRNAs to inhibit HIV infection (Nat Med. 8:681, 2002) and developed one of

the first lentiviruses for the delivery of siRNAs to non-dividing mammalian cells (RNA 9:493, 2003), which became the host vector for The RNAi Consortium’s collection of lentivirus-expressed siRNAs. Dr. Novina joined the faculty at Dana-Farber Cancer Institute and Harvard Medical School in 2004. Research The Novina Lab has been driven by two fundamental questions: (1) what is the mechanism by which microRNAs affect gene expression and (2) how does dysregulation of microRNA pathways influence oncogenesis? Using classical biochemistry, combinatorial biochemistry, systematic genomics, computational approaches and advanced technologies, Novina’s lab is elucidating the biology of microRNAs and their altered functions in disease. To address the aberrant hypo- and hyper-methylation of microRNA gene promoters that often occurs in cancers, the laboratory is developing “epigenetic engineering” tools based on CRISPR-Cas9 that will enable site-specific addition and removal of methyl groups on DNA to probe the effects of such methylation. This approach uses methyltransferases or demethylases that have been fused to a modified Cas9. The laboratory is using these tools to study how promoter methylation corresponds to changes in chromatin and transcription factor binding, and how methylation affects cancer phenotypes. The therapeutic implications are great: epigenetic reprogramming should lead to durable repression or activation of the targeted genes, with potential therapeutic applications in oncology via repression of oncogenes, induction of tumor suppressors, and reprogramming of leukocytes for improved anti-cancer immunotherapy. Novina’s strategy for epigenetic reprogramming also has potential beyond cancer. Interests: Epigenetics, CRISPR-Cas 9, cancer immunotherapy, microRNAs, methylation Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/labs/rnai

GIOVANNI PARMIGIANI, PhD Chair, Department of Biostatistics and Computational Biology Professor of Biostatistics, Harvard T.H. Chan School of Public Health Associate Director for Population Sciences, DF/HCC

Biography Dr. Parmigiani received his BS in Economics in 1984 from University L. Bocconi in Milano, Italy. He received his MS in 1987 and his PhD in 1990 from Carnegie-Mellon University, both in Statistics. Since joining Harvard in 2009, he has held several leadership roles: he is the Associate Director for Population Sciences of the multi-institutional Dana-Farber/Harvard Cancer Center, and he was formerly the Leader of its Biostatistics and Computational Biology Program (now Cancer Data Sciences Program). He is the Chairman of the Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute and is the director of the postdoctoral training grant in Quantitative Sciences for Cancer Research at the Harvard T.H. Chan School of Public Health, where he is a Professor.

Research Dr. Parmigiani is a statistician with a passion for and a demonstrated dedication to interdisciplinary cancer science, grounded on two decades of collaborative work across a broad spectrum of population, clinical, and basic cancer research. His work creates statistical tools for understanding cancer data, with particular focus on genetic epidemiology and genomics. He has a strong personal commitment specifically to rapid progress in familial risk assessment, from his own family history of colorectal cancer. Some of Dr. Parmigiani’s research interests include:

Models and software for predicting who is at risk of carrying genetic variants that confer susceptibility to cancer, with application to breast, ovarian, colorectal, pancreatic and skin cancer.

Statistical methods for the analysis of high-throughput genomic data: analysis of cancer genome sequencing projects; integration of genomic information across technologies; cross-study validation of genomics results.

Statistical methods for complex medical decisions: comprehensive models for lifetime history of chronic disease outcomes; decision trees and dynamic programming.

Bayesian modeling and computation: multilevel models; decision theoretic approaches to inference; sequential experimental design, Markov chain Monte Carlo methods.

Interests: Genetic epidemiology, Genomics, Risk Assessment

Publications: View publications in PubMed

Lab: http://bcb.dfci.harvard.edu/~gp/

DAVID S. PELLMAN, MD Margaret M. Dyson Professor of Pediatric Oncology Professor of Cell Biology, Harvard Medical School Investigator, Howard Hughes Medical Institute

Biography Dr. Pellman received his MD in 1986 from the University of Chicago, Pritzker School of Medicine, and did postgraduate training in pediatrics and pediatric hematology-oncology at DFCI and Children's Hospital, Boston. He was a postdoctoral fellow at the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology. In 1995, he joined DFCI, and is currently the Margaret M. Dyson Professor of Pediatric Oncology, Professor of Cell Biology, Harvard Medical School. In 2008, he was appointed as an Investigator of the Howard Hughes Medical Institute.

Research Dr. Pellman’s lab is interested in how cell cycle signals regulate chromosome segregation and polarized morphogenesis. Their experimental approaches include a combination of biochemical, genetic and live-cell imaging. There are ongoing projects using both yeast and animal cell systems. One area of interest for the lab is the mechanism of anaphase B. Many of the proteins involved in anaphase have been identified through genetic screens. One conserved component of the central spindle identified in Dr. Pellman’s lab has been purified and its in vitro properties are being characterized. The goal of this work is to understand how the half spindles are held together and how the spindle is disassembled at the end of mitosis. A related project concerns the regulation of spindle function by the cyclin degradation machinery (anaphase promoting complex or APC). Several spindle proteins are degraded through the APC at different times during the cell cycle. They are working on the mechanisms regulating the timing of these degradation events. A second area of interest is how polarity factors determine the position of the spindle within the cell. Spindle position is regulated during the development of many organisms in order to generate asymmetric cell divisions. Establishing spindle position involves capture of astral microtubules by poorly defined cortical proteins. Through genetic screens they have identified cortical cytoskeletal proteins and G-protein regulators necessary for determining spindle position. Dr. Pellman hopes to develop a mechanistic understanding of this process by studying the biochemical interactions between these proteins. Interests: Cell Division and Genome Stability Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/pellmanlab/

KORNELIA POLYAK, MD, PhD Professor of Medicine, Harvard Medical School Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute

Biography Dr. Polyak received her MD in 1991 from Albert Szent-Gyorgyi Medical University, Szeged, Hungary, and her PhD in 1995 from Cornell University/Memorial Sloan-Kettering Cancer Center. She completed a research fellowship in oncology at the Johns Hopkins Oncology Center in Baltimore, MD, where she studied the mechanisms of p53-mediated cell death. Joining DFCI in 1998, she is principally involved in basic laboratory research focused on cancer genetics and the molecular basis of breast cancer. Research Research in Dr. Polyak’s laboratory is dedicated to the molecular analysis of human breast cancer, studying breast tumors as

ecosystems and applying ecological and evolutionary methods to better understand the clinical implications of tumor heterogeneity. Her goal is to identify differences between normal and cancerous breast tissue, determine their consequences, and use this information to improve the clinical management of breast cancer patients. They have devoted much effort to develop new technologies that allow for the comprehensive molecular profiling of cells isolated from primary human tissue samples. Using these methods, their studies are at the forefront of the analysis of purified cell populations from normal and neoplastic human breast tissue at genomic scale and utilizing interdisciplinary approaches for the better understanding of clinical breast cancer. Dr. Polyak’s lab has characterized cells with stem cell characteristics from normal mammary epithelium and breast carcinomas. In the normal breast, they have been investigating molecular alterations induced by factors that influence breast cancer risk including pregnancy, breast density, and hereditary mutations in breast cancer genes with the aim of better understanding these changes and exploiting them for breast cancer preventative approaches. In breast cancer, they have been analyzing mechanisms that underlie intra-tumor heterogeneity including genetic, epigenetic, and non-hereditary changes, and the clinical consequences of intra-tumor diversity with special emphasis on tumor progression and therapeutic responses. Interests: Molecular Basis of Breast Tumor Evolution Publications: View publications in PubMed

BRENDAN D. PRICE, PhD Assistant Professor of Radiation Oncology, Harvard Medical School

Biography Dr. Price received his PhD in 1985 from the University of Cambridge and his postdoctoral training at the Royal Marsden Hospital, London, and the University of Glasgow, Scotland. He has performed research into control of cellular signaling by the ras and p53 proteins. He joined DFCI in 1992 and currently performs basic laboratory research aimed at understanding how the ATM protein regulates the cellular response to radiation therapy. Research The inherited disease ataxia-telangiectasia (AT) is characterized by numerous defects, including increased sensitivity to radiation, defective DNA repair, loss of DNA damage-induced signaling pathways, and

aberrant cell cycle control. The ATM protein, encoded by the AT gene, is a large protein kinase. ATM can phosphorylate many proteins involved in the two key responses to DNA damage - the activation of cell cycle checkpoints and the regulation of DNA repair. The ATM protein is therefore essential for coordinating the cells response to DNA damage. A major effort in Dr. Price’s laboratory is to identify how the ATM protein detects DNA damage and to determine how ATM relays this information to the DNA repair machinery. Price and his team have identified several essential motifs within the ATM protein structure, including a leucine zipper domain, which mediates protein-protein interactions, as well as an essential substrate binding domain located at the N-terminal of the ATM protein. Recently, they have identified a novel signaling pathway in which the activation of the ATM protein in response to DNA damage involves acetylation of ATM. The Price Laboratory’s long term goal is to develop small molecule inhibitors of the enzymes which control histone methylation and demethylation as potential therapeutic agents. By modifying the levels of histone methylation in tumor cells, they expect to be able to manipulate the ability of cells to repair DNA damage, and therefore sensitize cells to chemotherapy or radiotherapy. Developing epigenetic therapy to directly modulate DNA repair pathways in tumor cells is therefore expected to lead to new therapies to treat cancer. Interests: How the ATM Protein Regulates the DNA Damage Response Publications: View publications in PubMed Lab: http://pricelab.weebly.com/

JUN QI, PhD Lead Scientist, Department of Cancer Biology, Dana-Farber Cancer Institute

Biography Dr. Qi received his BS from Fudan University in China, and obtained his PhD in Chemistry from University of Michigan in 2006. He completed his postdoctoral training at MIT in 2009. Research Dr. Jun Qi is a Lead Scientist in the Medical Oncology Department and is the lead chemist in Dr. James Bradner’s laboratory at Dana-Farber Cancer Institute. Both his PhD and postdoctoral studies have been focused on the total synthesis of natural compounds and novel synthetic methodology development. Dr. Qi’s studies have been focusing on design and synthesis of small molecule inhibitors targeting the gene regulation pathway for cancer therapy. Dr. Qi has

discovered a small molecule JQ1 that inhibits one of the bromodomain subfamily, BET bromodomain. He is leading the effort to develop a chemical biology platform to understand the fundamental roles of epigenetic writer, reader and eraser. Interests: Total synthesis and methodology development, Drug Discovery, Lead Optimization, Assay Development Publications: View publications in PubMed

DAVID REARDON, MD Clinical Director, Center for Neuro-Oncology Physician Professor of Medicine, Harvard Medical School

Biography Dr. Reardon received his MD from Tufts University School of Medicine in 1986. He completed his postgraduate residency in Pediatrics at Johns Hopkins Hospital in 1989. He completed his fellowship at University of Michigan MOTT Children’s Hospital, in Pediatric Hematology/Oncology in 1992. Dr. Reardon ran a laboratory at St. Jude Children’s Research Hospital dedicated to identifying genetic abnormalities in pediatric brain tumors and conducting clinical research until 1998. He then joined the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke University from 2000-2011 as an adult neuro-oncologist, leading daily clinical/translational research operations as Associate Deputy Director. Dr. Reardon joined the Center of Neuro-Oncology at DFCI in 2011.

Research Dr. Reardon has lead preclinical studies evaluating immune based therapies using an orthotopic, immunocompetent glioblastoma model, in collaboration with colleagues from the DFCI cancer immunology group including Gordon Freeman and Glenn Dranoff. Results of this work have supported development of several clinical trials which are anticipated to initiate soon. In addition, this work led to the award of a $1.5-million-dollar grant for from the Ben and Catherine Ivy Foundation to expand preclinical and clinical efforts. Dr. Reardon has also been awarded funding from pharmaceutical companies for preclinical studies evaluating pipeline agents in glioblastoma animal models. Dr. Reardon has helped significantly expand the clinical research portfolio of the Center for Neuro-Oncology. He currently serves as principal investigator for 6 clinical trials that he opened in the past year. His additional accomplishments since coming to DFCI include: 1) publishing 50 peer-reviewed manuscripts; 2) conducting a neuro-oncology CME program for community neuro-oncologists that has become an annual endeavor; 3) leading separate institutional workshops on cutting edge therapies for meningioma patients and immunotherapy for glioblastoma. In November 2013, Dr. Reardon was elected President of the Society for Neuro-Oncology, the major society in the field. Interests: Brain and spinal tumors, Clinical trials in neuro-oncology, Targeted therapies, Anti-

angiogenic treatments, Immunotherapy, Convection-enhanced delivery

Publications: View publications in PubMed

ELLIS L. REINHERZ, MD Professor of Medicine, Harvard Medical School

Biography Dr. Ellis Reinherz received his MD from Harvard Medical School in 1975. After an internship and residency at Massachusetts General Hospital from 1975-1977 and a period as a hematology fellow at Brigham and Women's Hospital from 1977-1978, he joined DFCI. In addition to serving as chief of the Laboratory of Immunobiology, he is now director of the newly formed Cancer Vaccine Center. Research Dr. Reinherz’s laboratory continues to focus on T lymphocyte recognition of antigen as well as the process of T cell activation and differentiation. Particular emphasis has been placed on studying the structure-function relationship of the T cell receptor (TCR) for antigen

in major histocompatibility complex (MHC) products (CD3-Ti), CD2 and CD4. A multi-disciplinary approach involving x-ray crystallography and NMR technologies as well as cellular immunology and molecular biology is employed. Interests: Molecular Mechanisms of T Cell Recognition Publications: View publications in PubMed

JEROME RITZ, MD Executive Director, Connell and O'Reilly Families Cell Manipulation Core Facility Director for Clinical Trials Cores, Cancer Vaccine Center Professor of Medicine, Harvard Medical School

Biography Dr. Ritz received his MD from Chicago Medical School in 1972, followed by residency in internal medicine at the University of Wisconsin Hospital and Clinics, Madison. He completed a clinical fellowship in hematology and oncology at Beth Israel Hospital, and a research fellowship at DFCI, where he joined the staff in 1980. Since 1996, he has been director of the Connell and O'Reilly Families Cell Manipulation Core. Research Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used in the treatment of patients with hematologic malignancies, but continues to be associated with severe toxicities. Both the

effectiveness and toxicity of HSCT are mediated by donor T cells in the stem cell graft. Those T cells that target antigens expressed on recipient leukemia cells play an important role in eradicating residual tumor cells and preventing leukemia relapse after transplant. In contrast, T cells that target antigens expressed by normal tissues in the recipient are the primary mediators of graft-versus-host disease (GVHD) and thus lead to substantial toxicities. Dr. Ritz’s laboratory has focused on the assessment of donor immune function after HSCT and characterization of the immune mechanisms responsible for graft-versus-leukemia (GVL) and GVHD. Interests: Stem cell/bone marrow transplant, Tumor immunology Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/ritz_lab/

WILLIAM R. SELLERS, MD Senior Advisor to the President for Experimental Therapeutics at Dana-Farber Cancer Institute Core institute Member the Broad Institute

Biography Dr. Sellers earned his BS in biology from Georgetown University and his MD from University of Massachusetts Medical School. He completed his internship and residency in internal medicine at University of California San Francisco before completing a clinical oncology fellowship at Dana-Farber. William Sellers is a core institute member of the Broad Institute of MIT and Harvard, a faculty member at Harvard Medical School (HMS), and faculty member and senior advisor to the president for experimental therapeutics at Dana-Farber Cancer Institute (DFCI). Previously, Sellers served as vice president and global head of oncology at Novartis Institutes of BioMedical Research.

Research Dr. Sellers’s research efforts focus on investigating the basic mechanisms of tumor suppressor genes and oncogenes, and elucidating the molecular pathways of cancer, through high-throughput genetic sequencing and other genomics approaches. Notably, Dr. Sellers collaborated with his DFCI and Broad colleague Matthew Meyerson to lead the Broad’s first major foray into cancer genome sequencing. Their work, as well as work by other groups including investigators at Massachusetts General Hospital, led to the identification of EGFR mutations in lung cancer—a finding that helped pave the way for EGFR-inhibiting drugs becoming standard-of-care for patients. In addition, Dr. Sellers’s efforts to understand the genetic alterations in prostate and other cancers contributed to the discovery of MITF as an important gene in the development of melanoma. Interests: Cancer genomics, therapeutic discovery Publications: View publications in PubMed

GEOFFREY SHAPIRO, MD, PhD Director, Early Drug Development Center Clinical Director, Center for DNA Damage and Repair Senior Physician Associate Professor of Medicine, Harvard Medical School

Biography Dr. Shapiro received his PhD in 1987 and his MD in 1988 from Cornell University, followed by postgraduate training in internal medicine at Beth Israel Hospital, Boston, where he served as chief medical resident. Dr. Shapiro completed a fellowship in medical oncology at Dana-Farber Cancer Institute, during which he investigated the role of cell-cycle-related proteins in lung cancer. He joined the Dana-Farber faculty in 1994. Research Cyclin-dependent kinases (CDKs) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic

events cause universal overactivity of the CDKs in human cancer, and their inhibition frequently leads to cell cycle arrest, depletion of transcripts with short half-lives, and apoptosis. Using siRNA technology, Dr. Shapiro and his team have recently shown that depletion of both cell cycle and transcriptional CDK activities induces apoptosis in transformed cells. A primary focus of his laboratory is the characterization of CDK inhibitor drugs that mimic these effects. They are investigating both pan-CDK inhibitors, including flavopiridol, as well as inhibitors more selective for CDK 1 and 2. These compounds induce p53-independent apoptosis in transformed cells and modulate phosphorylation of Rb, p27(Kip1) and E2F-1. Dr. Shapiro’s team is designing pharmacodynamic assays to assess their biologic effects in tumors as early-phase trials begin. In addition, they have found that CDK inhibition is synergistic with DNA damage in inducing cancer cell death. CDK inhibition following cell-cycle disruption by chemotherapy drugs may alter the activity of the transcription factor E2F-1, thereby activating apoptosis pathways. Interests: Developmental therapeutics, Phase 1 clinical trials, Solid tumors, Cyclin-dependent kinase Publications: View publications in PubMed

MARGARET A. SHIPP, MD Chief, Division of Hematologic Neoplasia, Dana-Farber Cancer Institute Director, Lymphoma Program, Dana-Farber Cancer Institute Professor, Medicine, Harvard Medical School

Biography Dr. Shipp received her MD in 1979 from Washington University School of Medicine, St. Louis, where she also completed an internship and residency in internal medicine at Barnes Hospital. Her research focuses on the biology of normal and malignant B cells and aggressive B-cell lymphomas. Dr. Shipp is the Chief of the Division of Hematologic Neoplasia at DFCI, the Director of the Lymphoma and Myeloma Program of the Dana-Farber/Harvard Cancer Center and a Professor of Medicine at Harvard Medical School.

Research Dr. Shipp’s research and clinical interests are primarily in the area of aggressive B-cell non-Hodgkin's lymphomas. In the laboratory, Dr. Shipp seeks to identify cellular and molecular features which contribute to the unique natural histories of clinically relevant subsets of patients with aggressive B-cell lymphomas. These laboratory-based initiatives are closely integrated with longstanding clinical efforts to identify and treat subsets of patients whose aggressive B-cell lymphomas have very different natural histories. Another major area of emphasis in the laboratory is the interaction between tumor cells and surrounding stroma and the development of a conducive tumor microenvironment. Dr. Shipp has also developed in vitro models to analyze the events associated with the interaction between epithelial carcinoma cells and stromal elements and have begun to develop similar informative in vitro models for the interaction between aggressive B-cell lymphomas and relevant stromal components. Interests: Bone marrow transplantation, Lymphoma, Hodgkin disease Publications: View publications in PubMed Lab: http://shipplab.dfci.harvard.edu/

ROBERT J. SOIFFER, MD Chair, Executive Committee for Clinical Programs Vice Chair, Department of Medical Oncology Chief, Division of Hematologic Malignancies Co-Chief, Stem Cell Transplantation Institute Physician

Biography Dr. Soiffer graduated from New York University School of Medicine in 1983 and trained in internal medicine at Brigham and Women's Hospital, where he was chief medical resident. He joined DFCI in 1988 after completing a medical oncology fellowship. Dr. Soiffer is chairman of the Center for International Blood and Marrow Transplant Research advisory committee and has served as vice president (2006), president (2007), and immediate past president (2008) of the American Society of Blood and Marrow Transplantation. Research

Dr. Soiffer’s research activities focus upon modulation of the immune system in the treatment of cancer patients, most notably leukemias and lymphomas, but also more recently, melanoma and other solid tumors. Dr. Soiffer and his colleagues have concentrated their efforts on clinical strategies to reduce the incidence and severity of graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. They have conducted several clinical trials utilizing T12, a monoclonal antibody reactive with CD6+ T cells. They demonstrated that CD6+ T cell depletion of donor marrow, as the sole form of immune suppression, can decrease GVHD and transplant related mortality in patients receiving grafts from both related and unrelated donors. They have also developed clinical strategies to address the issue of relapse after transplantation. These have included the introduction of both cytokines (IL-2) and cellular elements (CD4+ donor cells) to both prevent and treat relapse. Dr. Soiffer’s lab is exploring the role of regulatory T cells (Tregs) in the development of GVHD and GVL reactions, and have initiated a clinical trial to augment GVL reactivity using an antibody to CTLA4Ig, a molecule that controls immune reactions. Dr. Soiffer has participated in clinical trials to induce autologous anti-tumor immunity. Working with Dr. Glenn Dranoff, Dr. Soiffer and his colleagues documented the generation of tumor immunity through vaccination of melanoma patients with irradiated autologous tumor cells genetically engineered to secrete GM-CSF. The team is combining vaccine approaches with the administration of allogeneic donor stem cells in hopes of inducing a synergistic anti-leukemia effect. Interests: Stem cell/bone marrow transplantation, Leukemia, Lymphoma, Chronic lymphocytic leukemia Publications: View publications in PubMed

BRUCE M. SPIEGELMAN, PhD Stanley J. Korsmeyer Professor of Cell Biology and Medicine, Harvard Medical School

Biography Bruce Spiegelman came to Harvard Medical School and the Dana-Farber Cancer Institute as an Assistant Professor, and was appointed Professor in 1991. Dr. Spiegelman received a B.S. with highest honors from the College of William and Mary, and a Ph.D. from Princeton University. His graduate work was immediately followed by postdoctoral research at the Massachusetts Institute of Technology. Dr. Spiegelman was elected to the National Academy of Science in 2002. Research Dr. Spiegelman’s lab is focused on the regulation of energy homeostasis in

mammals, primarily at the level of gene transcription. This includes the problems of fat cell development, control of metabolic rates and the pathways of glucose and lipid metabolism. These studies have applications to the development of new therapies for diabetes, obesity, muscular and neurodegenerative diseases. Most recently, Dr. Spiegelman’s lab has shown that PGC-1 beta is induced in liver by diets high in saturated and trans fats, and that this coactivator is largely responsible for the subsequent elevation in blood cholesterol and triglyceride synthesis. Current projects center on how the PGC-1 coactivators function mechanically by recruiting chromatin-modifying enzymes. The lab is also exploring the genetic role of the PGC-1 coactivators in a variety of metabolic states, including obesity, diabetes, muscle wasting, and nerve degeneration. They are particularly interested in how the PGC-1 coactivators control a variety of mitochondrial processes, including oxidative phosphorylation and the detoxification of reactive oxygen species (ROS), which are endogenous agents involved in aging and cancer, a very important area of future research. Interests: Differentiation of Human Tumors Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/spiegelmanlab/

KIMBERLY STEGMAIER, MD Co-Director of the Pediatric Hematologic Malignancy Program Physician Associate Professor of Pediatrics, Harvard Medical School

Biography Dr. Stegmaier is an Associate Professor of Pediatrics at Harvard Medical School, the Ted Williams Investigator and Vice Chair of Research in Pediatric Oncology at the Dana-Farber Cancer Institute (DFCI), and an Attending Physician at the Boston Children’s Hospital (BCH) and DFCI. She is the Co-director of the Pediatric Hematologic Malignancies Program at DFCI and BCH and is also an Institute Member of the Broad Institute. She received her B.S. from Duke University and her M.D. from Harvard Medical School. She completed her residency at BCH and a post-doctoral pediatric hematology-oncology fellowship at DFCI/BCH. In 2006, she launched her own laboratory effort at DFCI.

Research Dr. Stegmaier’s research program focuses on the integration of “omic” approaches for the identification of new protein targets and small-molecule modulators of malignancy with an eye toward clinical translation. Cancer discovery efforts in her laboratory have focused on the alteration of the malignant state (e.g., AML and neuroblastoma differentiation) and the modulation of pharmacologically challenging oncoproteins (e.g., EWS/FLI in Ewing sarcoma, MYCN in neuroblastoma, and NOTCH1 in T-ALL.) Most recently, Dr. Stegmaier and her colleagues are applying an integrated approach to discover new therapeutic opportunities in these malignancies with deep genomic characterization of primary tumors, kinase activity profiling for immediately druggable targets, functional genomic screening for new tumor dependencies and chemical screening for modulators of relevant oncogenic drivers. Clinical trials for patients with AML and Ewing sarcoma have resulted from their research and a trial testing BET bromodomain inhibitors in patients with MYCN amplified neuroblastoma is in development. Interests: Chemical screening, Neuroblastoma, Ewing Sarcoma, Hematologic malignancies, Cancer genomics Publications: View publications in PubMed

RICHARD M. STONE, MD Chief of Staff Program Director, Adult Leukemia Institute Physician Professor of Medicine, Harvard Medical School

Biography Dr. Stone received his MD in 1981 from Harvard Medical School and completed his internal medicine residency training at Brigham and Women's Hospital, along with a hematology-oncology fellowship at DFCI. He has performed numerous laboratory and clinical studies on acute leukemia and related disorders and frequently participates in grand rounds worldwide. He is currently the Director of the Adult Acute Leukemia Program at DFCI, serves on the Medical Oncology Board of the American Board of Internal Medicine, and is vice chair of the Leukemia Core Committee for the national cooperative trials group Cancer and Leukemia Group B.

Research The research of Dr. Stone and his clinical team involves identifying novel targets involved in the pathophysiology of acute leukemia and myelodysplastic syndrome. Inhibition of the FLT3 tyrosine kinase, for example, may offer benefits in AML patients - especially those whose blasts have an activating mutation in the enzyme - similar to the success of imatinib in the treatment of patients with chronic myeloid leukemia (CML). After conducting several trials with FLT3 inhibitors as single agents in myeloid malignancies, they are now focusing on combining these drugs with chemotherapeutic agents. Their laboratory continues to explore the mechanism of leukemic transformation via mutated FLT3, especially regarding activation of downstream pathways such as protein kinase A or AKT, which may be involved in key aspects of leukemogenesis such as prevention of apoptosis and promotion of self-renewal. Other areas of clinical research include targeted therapy in T cell ALL based on inhibition of NOTCH activation, a common survival mechanism in such cells; application of intensive "pediatric-type" strategies in adults with ALL; and many novel drugs in AML and MDS including histone deacetylase inhibitors, NEDD-8 inhibitors, HSP90 inhibitors, MEK inhibitors, and others. Interests: Leukemia, myelodysplastic syndromes, myeloproliferative disorders Publications: View publications in PubMed

CHRISTOPHER SWEENEY, MBBS Associate Professor of Medicine, Harvard Medical School Senior Physician, Medical Oncology, Dana-Farber Cancer Institute

Biography Dr. Sweeney received his medical degree from the University of Adelaide, South Australia in 1992 and completed an internship at the Royal Adelaide Hospital. He did residency in internal medicine at Gundersen Lutheran Medical Center, La Crosse, Wisconsin and a fellowship in Hematology/Oncology at Indiana University Medical Center, where he was later appointed Associate Director for Clinical Research for the Simon Cancer Center. Dr. Sweeney joined the Lank Center for Genitourinary Oncology at DFCI and Harvard Medical School in 2009.

Research Dr. Sweeney is a Medical Oncologist at the Dana-Farber Cancer Institute. He is a member of the American Society of Clinical Oncology, the Eastern Cooperative Oncology Group-ACRIN, Alliance and the American Association for Cancer Research. Dr. Sweeney has focused his academic career on the management of genitourinary malignancies, including prostate, bladder, testis, and renal cell cancer. His research interest has been primarily focused on drug development. This has included (i) design and conduct of phase I trials of new agents or new combinations that assess the safety and distribution of the drug in the body as well as the anti-cancer activity of the therapy; (ii) assessment of genetic variants and blood markers to try and define signatures that identify patients who are destined to benefit from a therapy; (iii) design and conduct of phase 2 and 3 clinical trials with a focus on bladder and prostate cancer and (iv) drug discovery and evaluation in the laboratory to guide clinical trial design. Dr. Sweeney is a highly active contributor to his field, having served on the Editorial Board for ASCO’s Journal of Clinical Oncology and the Program and Cancer Education Committees of the American Society of Clinical Oncology. He has received peer reviewed funding from the National Institutes of Health and the Department of Defense. Dr. Sweeney is also a member of the Scientific Advisory Boards of biotech companies in the United States and Australia. Interests: Prostate cancer, Clinical trials, Testicular cancer, Bladder cancer, Kidney cancer, Hormone and chemotherapy Publications: View publications in PubMed

SAPNA SYNGAL, MD, PhD Director of Research, Center for Cancer Genetics and Prevention Director, Gastrointestinal Cancer Genetics and Prevention Clinics Director, Gastroenterology, Brigham and Women's Hospital Senior Physician Professor of Medicine, Harvard Medical School

Biography Dr. Syngal received her MD from McGill University in 1990 and completed her clinical training in Internal Medicine and Gastroenterology at Brigham and Women's Hospital. She received her MPH from Harvard School of Public Health and completed a research fellowship at the Harvard Education Program in Cancer Prevention. She joined DFCI in 1995. Research The major focus of Dr. Syngal's career has been the development of research, clinical and training programs focusing on the genetics, screening, and prevention of gastrointestinal malignancies. Dr. Syngal

has created research programs that study the effectiveness of novel technologies with the goal of providing patients and physicians with new tools for preventing cancer through clarification of personal risk, early detection, and the use of novel screening techniques. Her main research focus has been to evaluate the impact of new genetic discoveries as tools for cancer risk assessment and the study of genetic epidemiology of colorectal cancer. With the discovery of the mismatch repair genes, MSH2 and MLH1, she led one of the first groups to evaluate the prevalence of mutations in large clinical populations, demonstrating phenotypic differences between carriers of the two genes. Her group also reported a high prevalence of colorectal cancer in patients with germline mutations in the TP53 gene, leading to the inclusion of colonoscopy screening into the National Comprehensive Cancer Network guidelines for care of patients with the Li-Fraumeni syndrome. She has also made major contributions to the field of risk assessment for genetic syndromes through the development of a novel risk assessment web-based tool (the PREMM model) to predict the likelihood of carrying mutations in the MSH2, MLH1, and MSH6 genes. Interests: Cancer screening and prevention, Familial cancer syndromes, Gastrointestinal cancers Publications: View publications in PubMed

STEVEN P. TREON, MD, PhD Director, Bing Center for Waldenström’s Macroglobulinemia Senior Physician Professor of Medicine, Harvard Medical School

Biography Dr. Treon received a medical degree with honors from the Boston

University School of Medicine, and a master’s degree in biochemistry and a doctorate of philosophy in tumor immunology from the graduate school at Boston University Medical Center. Dr. Treon completed an internship and residency in internal medicine at Boston University Medical Center. He also completed a clinical fellowship in hematology and oncology at the Massachusetts General Hospital and a research fellowship at the Dana-Farber Cancer Institute and Harvard Medical School. He received certification from the American Board of Internal Medicine (ABIM) in Internal Medicine and Medical Oncology, and continues to maintain his ABIM certification in Medical Oncology.

Research

Dr. Treon’s research interests are focused on understanding the genetic basis and pathogenesis of

Waldenström’s Macroglobulinemia (WM), and the development of targeted therapeutics for this malignancy. Using whole genome sequencing, the Treon laboratory discovered the highly prevalent MYD88 L265P and CXCR4 WHIM mutations in WM, permitting the development of diagnostic molecular testing and targeted treatments for WM. Signaling work performed in the Treon laboratory established the critical role of Bruton’s Tyrosine Kinase (BTK) as a key mediator of MYD88 signaling in WM cells. This discovery enabled the first ever breakthrough designation by the U.S. FDA for the accelerated approval of the BTK inhibitor ibrutinib for the treatment of WM. Dr. Treon served as the principal investigator of the pivotal trial that supported the regulatory approval of ibrutinib by the U.S. FDA and European Medicines Agency for the treatment of WM. He has also been the principal investigator for other clinical trials that resulted in the adoption of many novel therapeutics and combination therapies for the treatment of WM.

Interests: Waldenström's macroglobulinemia Publications: View publications in PubMed

ELIEZER VAN ALLEN, MD Assistant Professor of Medicine at Harvard Medical School Associate Member at the Broad Institute of MIT and Harvard

Biography Dr. Van Allen studied Symbolic Systems at Stanford University, obtained his M.D. from UCLA, and completed a residency in internal medicine at UCSF before coming to Boston and completing a medical oncology fellowship at the Dana-Farber/Partners Cancer Care program. Dr. Van Allen is an Assistant Professor of Medicine at Harvard Medical School, a clinician at Dana-Farber/Partners Cancer Care, and an Associate Member at the Broad Institute of MIT and Harvard. Research Dr. Van Allen focuses on clinical computational oncology and

the development of algorithms to analyze and interpret genomic data for clinically focused questions. His research areas include:

Prospective clinical interpretation. A primary focus of Dr. Van Allen lab is the development and application of algorithms that analyze and interpret complex 'omics data from individual patients for prospective clinical uses. Clinical response to therapies. A key research area involves the 'omic characterization of tumor and germline samples from patients who exhibit a spectrum of responses to existing and emerging cancer therapies. Integrative genomics. Dr. Van Allen has carried out multiple efforts that emphasize the integration of somatic and germline sequencing data for multiple purposes, including expanding the understanding of how functional germline variants mediate response to cancer therapies, enabling discovery of new germline drivers of disease in patients with multiple primary tumors, and exploring ways that familial genomic studies may inform the cancer genome-environment relationship.

Interests: computational cancer genomics, massively parallel sequencing, precision cancer medicine, genomic data algorithm, cancer therapeutics resistance, Publications: View publications in PubMed Lab: http://vanallenlab.dana-farber.org/research.html

NIKHIL WAGLE, MD Medical Oncologist, Medical Oncology, Dana-Farber Cancer Institute Assistant Professor of Medicine, Harvard Medical School Associate Member, Broad Institute

Biography Dr. Wagle holds an M.D., Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology. His residency training was in internal medicine at Brigham and Women’s Hospital, where he also served as chief medical resident, and completed his fellowship training in hematology/oncology in the Dana-Farber/Partners program. Research Dr. Wagle’s laboratory focuses on translational cancer genomics and precision cancer medicine, with a particular interest in metastatic breast

cancer. The major goal of the laboratory is to use systematic genomic and molecular characterization of tumor samples from patients with cancer to better understand the molecular determinants of tumorigenesis, characterize mechanisms of therapeutic response and resistance, and identify novel characteristics of tumors that might aid in clinical decision-making. Interests: Breast cancer, cancer genomics, therapeutic resistance, precision/personalized cancer medicine Publications: View publications in PubMed

LOREN D. WALENSKY, MD, PhD Physician Professor of Pediatrics, Harvard Medical School

Biography Dr. Walensky received his MD and PhD degrees from Johns Hopkins University School of Medicine in 1997. He trained at the Boston Combined Residency Program in Pediatrics and then completed a fellowship in pediatric hematology-oncology at DFCI and Children's Hospital Boston in 2003. He is board-certified in general pediatrics and pediatric hematology-oncology. He joined DFCI in 2003 and was named medical director of the new Program in Cancer Chemical Biology in 2005. Research The Walensky laboratory focuses on the chemical biology of deregulated

apoptotic and transcriptional pathways in cancer. To achieve their objectives, Walensky’s lab takes a multidisciplinary approach that employs synthetic chemistry techniques, structural biology analyses, and biochemical, cellular, and mouse modeling experiments to systematically dissect the pathologic signaling pathways of interest. The Walensky Laboratory has developed and applied “stapled peptides” that preserve the structure of biologically-active peptides as new chemical probes and prototype therapeutics tointerrogate the BCL-2 family-regulated mitochondrial apoptosis pathway. For example, Dr. Walensky’s lab identified the elusive trigger site on pro-apoptotic BAX that mediates its direct activation by activator BH3-only proteins, generated full-length BAK for the first time and characterized its direct activation mechanism, and discovered that one of the most potent and selective inhibitors of anti-apoptotic MCL-1 is its own BH3-interaction domain. Most recently, Dr. Walensky found that the BH4 domain helix of BCL-2 can independently block pro-apoptotic BAX activation by targeting BAX at a novel interaction site. By interrogating BCL-2 family signaling proteins using a diversity of analytical approaches, the Walensky Lab aim to uncover the interaction surfaces and mechanisms that regulate apoptotic function. They strive to conduct structure-function studies that will advance our fundamental understanding of these oncogenic proteins so that new therapeutic strategies can be developed to overcome cancer chemoresistance. Interests: Hematologic malignancies Publications: View publications in PubMed Lab: http://research4.dfci.harvard.edu/walensky/

DAVID M. WEINSTOCK, MD Associate Professor, Medicine, Harvard Medical School Attending Physician, Medical Oncology Service, Dana Farber Cancer Institute Associate Member, Cancer Biology, Broad Institute

Biography Dr. Weinstock received his medical degree from George Washington University School of Medicine in 1997. He subsequently completed his residency in Internal Medicine at New York Hospital/Cornell, and his fellowship in Medical Oncology and Infectious Diseases at Memorial Sloan-Kettering Cancer Center. He joined the staff of Dana-Farber Cancer Institute and Brigham and Women's Hospital in 2008, where he is a medical oncologist and laboratory investigator in Hematologic Neoplasia. Research Dr. Weinstock directs a translational research program focused on

novel therapeutics for lymphoid malignancies. The laboratory utilizes both functional and sequencing approaches to identify and characterize oncogene alterations directly from tumor specimens. Newly-identified alterations are further assayed using a variety of in vitro and in vivo methods, with the ultimate goal of translating discoveries into novel therapies. Dr. Weinstock’s initial efforts identified CRLF2, a previously obscure cytokine receptor, as an essential oncogene in 5-10% of adult and pediatric acute lymphoblastic leukemia (ALL). He and his lab subsequently demonstrated that agents targeting HSP90 or BRD4 are active in human leukemias with CRLF2 alterations, defined the mechanisms of CRLF2 locus rearrangement and clarified mechanisms that link CRLF2 alterations with Down Syndrome. These findings have inspired clinical trials in both children and adults with this poor-risk subset of ALL. In a second line of inquiry, they are assaying the nature and determinants of DNA repair in mammalian cells. These studies extend from tumor specimens, where they have characterized a novel oncogene-DNA repair interaction, to human embryonic and induced pluripotent cells. Third, the Weinstock Lab utilizes ultra-deep sequencing of subpopulations sorted from bone marrow specimens to trace the ontogeny of specific alterations identified within lymphomas. Lastly, Dr. Weinstock founded PRoXe (Public Repository of Xenografts), an open-source website to disseminate information relevant to patient-derived xenografts (PDXs), particularly a library of PDX models generated from patients with cancer. Interests: Stem cell transplantation

Publications: View publications in PubMed

Lab: http://weinstock.dfci.harvard.edu/

ProXe: http://www.proxe.org/

BRIAN M. WOLPIN, MD, MPH Robert T. and Judith B. Hale Chair in Pancreatic Cancer, Dana-Farber Cancer Institute Co-Director, Pancreas and Biliary Tumor Center, Dana-Farber Cancer Institute Associate Professor of Medicine, Harvard Medical School Physician

Biography Dr. Wolpin received his medical degree from Harvard Medical School in 2001. He subsequently completed his residency in Internal Medicine at Brigham and Women's Hospital, and his fellowship in Medical Oncology at the Dana-Farber Cancer Institute. He joined the staff of DFCI and Brigham and Women's Hospital in 2007, where he is a medical oncologist and clinical investigator in the Center for Gastrointestinal Oncology. His research focuses on biomarkers and novel therapeutics in gastrointestinal malignancies, and mechanisms by which lifestyle factors interact with malignant risk and progression.

Research The research program of medical oncologist and Center Co-Director Brian Wolpin, focuses on understanding the factors that promote the development and growth of pancreatic and biliary cancer. His studies involve large-scale analyses of samples donated by hundreds to thousands of patients, with evaluation of factors in blood, inherited DNA changes, and DNA changes in tumors. The goal of his group's work is to define new ways to diagnose pancreatic biliary tumors early, and to treat them more effectively by targeting specific changes in individual tumors. His work has been published in the Journal of Clinical Oncology, Journal of the National Cancer Institute, Gastroenterology, Nature Genetics, Nature Medicine, and the New England Journal of Medicine. Dr. Wolpin serves as Principal Investigator for the Pancreatic Cancer Cohort Consortium, a National Cancer Institute consortium of more than 30 studies from around the world dedicated to understanding the causes of pancreatic cancer. He also directs a large pancreatic cancer specimen bank, which archives and analyzes blood and tumor specimens from patients at Dana-Farber, Brigham and Women’s Hospital, and other institutions around the United States. Dr. Wolpin serves on the Alliance/CALGB Gastrointestinal Cancer Committee, which sets national clinical trial priorities for pancreatic and biliary cancer. In addition, he serves on the NCCN Guidelines Committee for Pancreatic Adenocarcinoma, which sets guidelines used around the world for the standard treatment of patients with pancreatic cancer. Interests: Gastrointestinal cancers Publications: View publications in PubMed

CATHERINE J. WU, MD Associate Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute Institute Member, the Broad Institute

Biography Dr. Wu graduated from Harvard University with a degree in biochemistry, and earned her medical degree from Stanford University School of Medicine. She spent her residency in internal medicine at Brigham and Women’s Hospital and completed a postdoctoral fellowship in hematology-oncology at the DFCI/Partners CancerCare training program. Research Dr. Wu’s research is primarily focused on chronic lymphocytic leukemia (CLL). Her lab is using cutting edge genomic technologies to understand the underlying biology of the disease and to develop effective therapies.

This includes using next-generation, massively parallel sequencing technologies to identify and assess the potential functional effects of genetic mutations found within CLL cells. This information is used to identify novel, tumor-specific targets for immune-based treatment, and to develop a thorough understanding of the mutational landscape of CLL. Interests: Tumor antigens, chronic lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, stem cell transplantation, sickle cell anemia Publications: View publications in PubMed

KAI WUCHERPFENNIG, MD, PhD Chair, Department of Cancer Immunology and Virology Director, Center for Cancer Immunotherapy Research Professor of Neurology, Brigham and Women's Hospital and Harvard Medical School Professor of Microbiology and Immunobiology, Department of Microbiology and Immunobiology, Harvard Medical School

Biography Dr. Wucherpfennig received his MD in 1986 and his PhD in 1987 from the University of Goettingen, Germany. He completed research fellowships at Brigham and Women's Hospital and the Department of Molecular and Cellular Biology, Harvard University. In 1995, he joined DFCI, where he is principally involved in basic laboratory research that focuses on T cell immunology and the role of T cells in cancer immunology. Research Harnessing the power of T cells of the immune system in cancer could allow for the specific detection and selective destruction of cancer cells based on T cell receptor-driven recognition of tumor antigens. All therapeutic approaches that have shown efficacy in the clinic are

fundamentally based on enhancing the function of cytotoxic T cells. The Wucherpfennig lab is working to develop the next generation of cancer immunotherapies through the identification of the critical molecular switches controlling the ability of T cells to destroy cancers in highly immunosuppressive tumor microenvironments. Recently, Dr. Wucherpfennig reported a novel in vivo approach that enables discovery of negative regulators of T cell function in tumors. The genes identified provide an opportunity to enhance the anti-tumor activity of adoptive T cell therapies, for example with T cells that express a chimeric antigen receptor (CAR). Interests: cancer immunology, T cell therapies Publications: View publications in PubMed Lab: http://t-cells-treating-cancer.dana-farber.org/about-kai.html

BAOCHUN ZHANG, MD, PhD Assistant Professor of Medicine, Harvard Medical School Principal Investigator, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute

Biography After studying Medicine in China, Dr. Zhang obtained his PhD from the Medical University of Ohio. Dr. Zhang did his postdoctoral training with Dr. Klaus Rajewsky and Dr. Frederick Alt at the Immune Disease Institute and Children’s Hospital Boston, Harvard Medical School, where he focused on understanding the pathogenesis of diffuse large B cell lymphoma, and immune surveillance against Epstein-Barr virus-associated B cell lymphomas. Dr. Zhang is now an Assistant Professor at the Division of Hematologic Neoplasia of DFCI, and Harvard Medical School. Research

Dr. Zhang’s laboratory research effort proceeds along two directions. 1) Using genetically modified mice to study the molecular pathogenesis of diffuse large B cell

lymphoma (DLBCL) and Epstein-Barr virus-associated B cell lymphoma. Lymphomas derive from B cells acquiring multiple oncogenic events. Genetically engineered mice, carrying conditional gain- and/or loss-of-function mutants, allow Dr. Zhang to assess the causal role of each individual mutational event, the cooperation of multiple such events in lymphomagenesis, and to follow up disease dynamics in vivo. These studies form the basis for identification/validation of therapeutic targets, and rational design of combinatory therapies.

2) Using mouse models to reveal the surveillance mechanism of immune system on B cell lymphomas, with particular focuses on tumor-killing CD4+ T cells and their regulation by CD8+ regulatory T cells. This work guides efforts in Dr. Zhang’s lab to develop new immunotherapy strategies for B cell malignancies, and possibly other cancers as well.

Interests: Molecular pathogenesis and immune control of B cell lymphomas Publications: View publications in PubMed

Lab: http://zhanglab.dfci.harvard.edu/

JEAN ZHAO, PhD Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Professor, Cancer Biology, Dana-Farber Cancer Institute

Biography Jean Zhao received her PhD from Tufts University School of Medicine in 1999. She did her postdoctoral work in the laboratory of Dr. Thomas M. Roberts, became an Instructor in Medicine at Harvard Medical School in 2003, and joined the faculty of DFCI and Harvard Medical School in 2006. Research Dr. Zhao is interested in how kinases in general, and phosphatidylinositol 3-kinases (PI3K) in particular, control malignant transformation. The work of Dr. Zhao’s laboratory integrates molecular biology, tissue engineering and novel mouse models of human cancer to study oncogenic alterations in kinases that are

involved in primary tumor formation and metastasis. In addition to these unique genetically engineered mouse models, they have developed a number of additional experimental systems, including, synthetic human tumors, and kinome-wide libraries of activated kinases to elucidate the mechanisms by which kinases function in cancer. Dr. Zhao’s laboratory hopes these studies will allow them to harness the potential of these molecules as specific targets for cancer therapies. The PI3K pathway is a key signal transduction system that links oncogenes and multiple receptors to many essential cellular functions, which is tightly regulated by PI3Ks and the tumor suppressor PTEN. This pathway is perhaps the most commonly activated signaling pathway in human cancer, therefore presenting both an opportunity and a challenge for cancer therapy. Studies in Zhao’s group using genetic engineered mouse models of tissue-specific ablation of PIK3CA or PIK3CB begin to reveal distinct roles of these two isoforms in cellular signaling, metabolism, development and tumorigenesis, providing the framework and rationale for targeting selective isoforms of PI3K in cancer. They continue to define how these isoforms of PI3K function in different tumor types and tissues, and their individual and collective contributions to transformation. More importantly, they are striving to understand the underlying cellular and molecular pathways and programs that protect tumors with aberrant activation of PI3K from PI3K-targeted therapy to overcome the major challenge of resistance and improve therapeutic efficacy. Interests: Kinase signaling in cancer Publications: View publications in PubMed Lab: http://jeanzhao.dfci.harvard.edu/