IRHRM

The Institute for Reproductive Health and Regenerative Medicine

NEWSupdate ISSUE 5: February 2014

EXECUTIVE RESEARCH BOARDMichael J. Soares, PhD (Chair)

Merlin G. Butler, MD, PhD

Susan Carlson, PhD

T. Rajendra Kumar, PhD

Kenneth R. Peterson, PhD

Katherine F. Roby, PhD

Carl P. Weiner, MD, MBA

INTERNAL ADVISORY BOARDKenneth L. Audus, PhD

Paul F. Terranova, PhD

EXTERNAL SCIENTIFIC ADVISORY BOARDMarisa S. Bartolomei, PhD

C. Anthony Blau, MD

Martin M. Matzuk, MD, PhD

Bryan Richardson, MD

Yoel Sadovsky, MD

www.kumc.edu/irhrm

New CRS Director AppointedWe are pleased to announce the appointment of T. Rajendra Kumar, PhD, as the new Director of the Center for Reproductive Sciences (CRS). Dr. Kumar is an Associate Professor in the Department of Molecular & Integrative Physiology at KUMC. Dr. Kumar is a well-respected reproductive biologist whose research program is currently funded by 3 NIH grants. Dr. Kumar has some exciting ideas for strengthening the CRS, and we look forward to his input as a new member of the IRHRM Executive Research Board. Dr. Kumar earned his PhD at the University of Delhi in 1989. Dr. Kumar did his postdoctoral training in the Vollum Institute in Portland, Oregon from 1990-1993. He then moved to Baylor College of Medicine in Houston, Texas, where he rose in rank to Assistant Professor before being recruited to KUMC as an Assistant Professor in 2004. Dr. Kumar was promoted to Associate Professor with Tenure in July 2009. Dr. Kumar’s research focuses on development and regulation of the pituitary-gonadal axis using a variety of genetic approaches. His research is clinically relevant and has high translational research potential. His work will significantly impact our understanding of the physiology, pathology and aging of the mammalian pituitary-gonadal axis including abnormal pituitary/gonad development, infertility, and cancer of the pituitary and gonads. Dr. Kumar has published 80 papers including book chapters and invited reviews. Some of these were published in Nature, Nature Genetics, Cell, JCI, PNAS, Molecular Endocrinology and Endocrinology.

Please join us in congratulating Dr. Kumar on his appointment!

T. Rajendra Kumar, PhD

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Welcome New Members

Please join us in welcoming our 8 new members who joined the IRHRM since December of 2013!

Gustavo Blanco, MD, PhD, Professor of Molecular and Integrative Physiology, KUMC; the role of ion-transport proteins of the plasma membrane in cell function to help understand the importance of ion transport in male germ cell fetility and contraception

Vargheese Chennathukuzhi, PhD, Assistant Professor of Molecular and Integrative Physiology, KUMC; Investigating the biology of an aberrantly expressed G protein-coupled receptor that contributes to the fibroid’s tumor growth to develop small molecular and peptidomimetic drugs from the treatment of uterine fibroids

T. Rajendra Kumar, PhD, Associate Professor of Molecular and Integrative Physiology, KUMC; Developmental genetics and regulation of the pituitary-gonadal axis using both gain-of-function (transgenic) and loss-of-function (gene knockout) approaches to better understand the physiology and pathology of the mammalian pituitary-gonadal axis, including abnormal pituitary-gonadal development, infertility, and cancer of the pituitary and gonads. Stuart J. Macdonald, PhD, Director, Kansas INBRE KU Sattelite Bioinformatics Core, Associate Professor of Molecular Biosciences, University of Kansas - Lawrence; Studies the genetic control of complex, polygenic trait variation

Stephen J. Renaud, PhD, Research Assistant Professor of Pathology and Laboratory Medicine, KUMC; Studies the fundamental regulation of placental development, including transcriptional control of trophoblast differentiation and defining interactions between maternal immune cells and trophoblast cells

Marco Bortolato, MD, PhD, Assistant Professor of Pharmacology and Toxicology, University of Kansas - Lawrence; Research focuses on the characterization of the biological bases of neurodevelopmental disorders through the employment of behavioral tests in animal models. Key scientific interest is the identification of the mechanisms of interaction between lipid mediators (including neuroactive steroids and endocannabinoids) and key brain neurotransmitters, such as dopamine and serotonin.

Rama Garimella, PhD, MS, MSc, Research Assistant Professor of Hematology and Oncology, KUMC; Research focuses on understanding the mechanisms underlying osteosarcoma pathobiology.

Courtney Marsh, MD, MPH, Clinical Assistant Professor of Obstetrics and Gynecology; Research focuses on modification of known risk factors in women with polycystic ovary syndrome (PCOS) to reduce prevalence of PCOS related co-morbidities such as infertility, endometrial cancer, diabetes, cardiovascular disease, and obstructive sleep apnea.

CURRENT IRHRM MEMBERS: 83 researchers from 4 institutions, representing 28 academic departments -- 72 @ KUMC, 7 @ KU-Lawrence,

3 @ Kansas State University, and 1 @ UMKC/CMH.

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Merlin Butler, MD, PhD, FFACMG

Members In the News

Article on Prader-Willi syndrome makes pediatric journal’s top 100January 17, 2014

A University of Kansas School of Medicine physician-scientist contributed to one of the 100 most cited pediatric articles since 1945.

Merlin G. Butler, MD, PhD, a professor and clinical geneticist who holds appointments in the departments of Psychiatry and Behavioral Sciences and Pediatrics, co-authored a 1993 manuscript establishing the diagnostic criteria for Prader-Willi syndrome.

Prader-Willi syndrome is a rare non-inherited genetic disorder of chromosome 15 which causes children to have a constant sense of hunger and slower metabolic rates leading to obesity in early childhood which can be life threatening; learning disabilities, speech issues; and weak muscle tone. The syndrome occurs in approximately one out of every 12,000 to 15,000 births.

Butler worked with other clinicians experienced with the syndrome to develop the criteria. Their 1993 paper ranked No. 53 on the list of most cited pediatric publications. The number of citations, 618, is striking number given how rare Prader-Willi syndrome is.

The authors of the top 100 most cited list said there were 497,240 articles published in 191 pediatric journals between 1945 and 2010.

Butler continues to conduct extramurally

funded genetics and clinical research on Prader-Willi syndrome, Angelman syndrome, fragile X syndrome, autism and obesity.

http://www.kumc.edu/school-of-medicine/about-the-school/inside-the-school-of-medicine.html

New Strategic Initiative Grants support KU research on energy, human health, environmentFebruary 3, 2014

Article by Kevin Boatright, edited for IRHRM

newsletter by Stacy McClure

LAWRENCE — Three new University of Kansas research projects are the latest recipients of internal Strategic Initiative Grants, designed to achieve goals laid out in KU’s Bold Aspirations strategic plan. The three Level I projects address significant global challenges and will receive more than $982,000 in funding over the next three years.

Three IRHRM members, Marco Bortolato, MD, PhD, Merlin Butler, MD, PhD, FFACMG, and Ann Manzardo, PhD, MSCR, and, are involved in one of the three funded projects:

“Developing a Research Consortium on Aggression and Drug Abuse” ($383,174, three years) Participating researchers are Marco Bortolato, Merlin Butler,

Marco Bortolato, Merlin Butler & Ann Manzardo

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Members In the News / Histone-Chromatin GroupPaula Fite, Erik Lundquist and Ann Manzardo, representing the Department of Pharmacology and Toxicology, the Center for Molecular Analysis of Disease Pathways, the Clinical Child Psychology Program, the Department of Psychology and the Department of Psychiatry & Behavioral Sciences at KU Medical Center.

The consortium will be the first multi-disciplinary network in the country for studying how and why pathological impulsive aggression and substance abuse and addiction disorders exist concurrently but independently in a subject. Using a unique combination of clinical and preclinical studies, the goal is to develop effective preventive and therapeutic interventions.

“KU faculty and staff continue to make innovative proposals in response to this unique research opportunity,” said Jeffrey S. Vitter, provost and executive vice chancellor. “By making focused investments, KU is able to build competitive research capacity by forming multidisciplinary teams to work on important, high-priority problems.”

The three new projects involve 17 different researchers representing 12 different departments and centers at the Lawrence and Medical Center campuses. Each project is aligned with one or more of the Bold Aspirations strategic initiative themes: Sustaining the Planet, Powering the World; Promoting Well-Being, Finding Cures; Building Communities, Expanding Opportunities; and Harnessing Information, Multiplying Knowledge.

The Research Investment Council, which reviews all Level I Strategic Initiative Grant proposals, has now recommended 12 Level I awards totaling nearly $4.4 million since the program began in 2012. A number of smaller Level II awards have also been made. The final Level I proposal deadline

for the 2013-14 academic year is March 1.

https://news.ku.edu/2014/02/03/new-strategic-initiative-grants-support-ku-research-energy-human-health-and-environment

Histone-Chromatin Interest Group

Led by Joseph Fontes, PhD, the Histone-Chromatin Interest Group was formed to facilitate the exchange of new findings, technical approaches and bioinformatic expertise among interested investigators at KUMC. Meetings are held monthly (usually on Mondays) in Beller Conference Center, with an investigator presenting recent data from his or her laboratory. These are not formal seminar presentations; rather, the goal is to create a “lab meeting” like atmosphere, where presenters are comfortable sharing very recent work, incomplete stories, and/or technical hurdles broadly related to chromatin structure and function. The hope is that through these interactions the members of the group will benefit from others’ experience and knowledge and identify potential collaborations between laboratories. Such presentations are a good place to try out new ideas for grant proposals and solicit feedback/collaborations. The meetings are open to all laboratory members, not just PIs. The first two meetings featured Dr. Jeremy Chien (January) and Drs. Chad Slawson and Kenneth Peterson (February). Upcoming meetings will feature Dr. Luciano DiTacchio (March 31) and Dr. Udayan Upte (April 21). Contact Lesley Shriver, lshriver@kumc.edu, to be added to the email list for meeting announcements.

Joe Fontes, PhD

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New Grant Awards and Honors - Congratulations!

FACULTY GRANTS

Developing a Research Consortium on Aggression and Drug Abuse. Funded by: University of Kansas Research Investment Council: Level I Proposal. PI: M Bortolato, Co-I’s: MG Butler and A Manzardo, E Lundquist.

Genomic Characterization of Alcohol Dependence Phenotypes and Correlates in a Fifty Year High Risk Study of Male Alcoholism. Funded by, Heartland Institute for Clinical Translational Research – Special Opportunity for Research on Alcoholism, Alcohol Abuse and Dependency. PI’s EC Penick and MG Butler. Co-I A Manzardo

1 R01 DK100595-01, 01/01/14 – 12/31/16, $174,000 (Annual direct costs), $522,000 (Total direct costs), “Regulation of Globin Gene Switching by O-GlcNAc Post-Translational Modification,” Co-PIs KR Peterson and C Slawson

South West Oncology Group (SWOG) Development Grant award. Title: Pilot study exploring the use of hyperbaric oxygen in autologous PBSC transplantation. Duration: two years. PI: O Aljitawi

“Targeting FoxM1 signaling in ovarian cancer,” DOD, PI: J Chien

“Pre-Clinical Assessment of MCP-1/CCR2 Inhibition as Treatment for ADPKD,” Polycystic Kidney Disease Foundation, 3/1/14-2/28/16, PIs: TA Fields and KI Swenson-Fields

FACULTY HONORS & AWARDS

H Zhu - Reviewer for Diabetes UK (The British Diabetic Association) RD Lawrence Fellowship Application

J Wang - Panel Member, Department of Defense 2013 Peer Reviewed Medical Research Program, Osteoarthritis Research Program Review Panel, December 18-19, 2013

TRAINEE HONORS & AWARDS

Angela Pierce awarded 2014 K-INBRE Symposium poster award (Trainee with JA Christianson)

UPCOMING NIH GRANT APPLICATION DEADLINES

MARCH 5: R01 and U01 renewals,

resubmissions and revisions

MARCH 16: R03, R21 renewals, resubmissions and revisions

MAY 25: All P Series (P01)

JUNE 5: R01 and U01 new applications

As a reminder, the IRHRM administrative team is available to assist with the grant application

preparation and submission process. For assistance, please contact

Lesley Shriver, lshriver@kumc.edu or Stacy McClure,

smcclure@kumc.edu.

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Some Recent Publications

Groover AL, Ryals JM, Guilford BL, Wilson NM, Christianson JA, Wright DE. Exercise-mediated improvements in painful neuropathy associated with pre-diabetes in mice. Pain 2013; 154:2658-2667.

Yang F-C, Tan T, Huang T, Christianson JA, Samad OA, Liu Y, Roberson D, Davis BM, Ma Q. Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues. Cell Rep 2013; 5:1353-1364.

Manzardo AM, He J, Poje A, Penick EC, Campbell J, Butler MG. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence. Drug Alcohol Depend 2013;133:562-570.

Roberts JL, Hovanes K, Dasouki M, Manzardo AM, Butler MG. Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services. Gene 2014; 535:70-78.

Dasouki MJ, Rafi SK, Olm-Shipman AJ, Wilson NR, Abyankar S, Ganter B, Furness LM, Fang J, Calado RT, and Saadi I. Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia. Blood 2013;122:3440-3449.

Aljitawi OS, Li D, Xiao Y, Zhang D, Ramachandran K, Stehno-Bittel L, Van Veldhuizen P, Lin TL, Kambhampati S, Garimella R. A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of

leukemia cells. Leuk Lymphoma 2014; 55:378-391.

Wickersheim ML, Blumenstiel JP. Terminator oligo blocking efficiently eliminates rRNA from Drosophila small RNA sequencing libraries. Biotechniques 2013; 55:269-272.

Tan EP, Caro S, Potnis A, Lanza C, Slawson C. O-linked N-acetylglucosamine cycling regulates mitotic spindle organization. J Biol Chem 2013; 288:27085-27099.

Rajendran G, Dutta D, Hong J, Paul A, Saha B, Mahato B, Ray S, Home P, Ganguly A, Weiss ML, Paul S. Inhibition of protein kinase C signaling maintains rat embryonic stem cell pluripotency. J Biol Chem 2013; 288:24351-24362.

Renaud SJ, Kubota K, Rumi MA, Soares MJ. The FOS transcription factor family differentially controls trophoblast migration and invasion. J Biol Chem 2014; 289:5025-5039.

Blumenstiel JP, Chen X, He M, Bergman CM. An age-of-allele test of neutrality for transposable element insertions. Genetics. 2014; 196:523-538.

Aljitawi OS, Xiao Y, Eskew JD, Parelkar NK, Swink M, Radel J, Lin TL, Kimler BF, Mahnken JD, McGuirk JP, Broxmeyer HE, Vielhauer G. Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced human CD34+ cells in a murine model of umbilical cord blood transplantation. Blood Cells Mol Dis 2014; 52:59-67.

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Upcoming Event Highlights The Annual James L. Voogt Lecture in Neuroendocrinology - Thursday, February 27

Please join us on February 27 for the Annual James L. Voogt Lecture in Neuroendocrinology, being held from 8:30 - 9:30 am in the Lied Auditorium. Andrea C. Gore, PhD, Gustavus and Louise Pfeiffer Professor

of Pharmacology and Toxicology at the University of Texas, Austin, will present a lecture titled”Are Environmental Endocrine Disruptors Impairing Reproduction, Brain and Behavior?”

The Annual Voogt Lectureship honors Dr. James L. Voogt, an emeritus faculty member of KUMC whose research career focused on Neuroendocrinology. Dr. Voogt will be present during the lecture and we hope you will join us!

The Inaugural Ivan Damjanov Lecture in Stem Cell Research - Thursday, March 27

It is with great pleasure that we announce the Inaugural Ivan Damjanov Lecture in Stem Cell Research. On March 27 at 8:30 am in the Lied Auditorium, Peter W. Andrews, PhD, The Arthur Jackson Professor of

Biomedical Science, Centre for Stem Cell Biology, at the University of Sheffield in Great Britain, will present a lecture titled “Did Embryonic Stem Cells Come from Mars?”

The Annual Ivan Damjanov Lecture in Stem Cell Research honors Ivan Damjanov, MD, PhD, Professor of Pathology at KUMC, who made early contributions to the understanding of stem cell biology. Please plan to attend!

The Annual Donald C. Johnson Lecture in Reproduction - Thursday, April 3

Richard L. Stouffer, PhD, Senior Scientist and Chief, Division of Reproductive and Developmental Sciences at Oregon National Primate Research Center/Oregon Health and Science

University, will be giving the Annual Donald C. Johnson Lecture in Reproduction on Thursday, April 3 from 8:30-9:30 a.m. in the Lied Auditorium. His talk is titled “The Primate Ovary as a Model for Understanding and Treating Infertility”.

The Johnson Lectureship honors the reproductive biology research career of former KUMC faculty member Donald C. “DC” Johnson.

Andrea Gore, PhD

James Voogt, PhD

Peter Andrews, PhD

Ivan Damjanov, MD, PhD

Richard Stouffer, PhD

Donald C. Johnson, PhD

Save the Date! Greenwald

Symposium, Nov. 6-7, 2014

The 11th Annual Gilbert S. Greenwald Symposium on Reproduction and Regenerative

Medicine will be held November 6-7, 2014. Our keynote lecturer is W. Lee Kraus, PhD,

Endowed Professor and Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences at UT Soutwhestern Medical Center.

MORE DETAILS COMING SOON!

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Upcoming Events (February - May 2014)

February 2014

27 Annual James L. Voogt Lecture in Neuroendocrinology, 8:30 - 9:30 am, Lied Aud., Andrea C. Gore, PhD, University of Texas, Austin, Are Environmental Endocrine Disruptors Impairing Reproduction, Brain and Behavior? Host: Katherine F. Roby

March 2014

5 * CRS Chalk Talk, Noon, 3070 HLSIC, Nancy Muma, PhD, Regulation of Serotonin Receptor Signaling by Estrogens

13 Seminar, 8:30 - 9:30 am, Lied Aud., Clodia Osipo, PhD, Loyola University, Regulation of Notch Signaling in HER2+ Breast Cancer: Therapeutic Implications Host: Joan Lewis-Wambi

19 CESCB Chalk Talk, Noon, 3070 HLSIC, Animesh Dhar, PhD, JMJD1a: A Possible Target for Pancreatic Cancer Therapy

27 Inaugural Ivan Damjanov Lecture in Stem Cell Research, 8:30 - 9:30 am, Lied Aud., Peter Andrews, PhD, University of Sheffield, Did Embryonic Stem Cells Come from Mars? Host: Ivan Damjanov

31 Histone-Chromatin Interest Group Meeting, 4-5 p.m., 1001-1003 Beller Conference Center; Luciano DiTacchio, PhD, presenting (title TBD)

April 2014

3 Annual Donald C. Johnson Lecture in Reproduction, 8:30-9:30 a.m., Lied Aud., Richard L. Stouffer, PhD, Oregon Health & Science University, The Primate Ovary as a Model for Understanding and Treating Infertility, Host: Michael J. Soares

4 * CESCB Chalk Talk, Noon, 3070 HLSIC, Jinxi Wang, MD, PhD, Title TBD

9 * CESCB Chalk Talk, Noon, 3070 HLSIC, Jay L. Vivian, PhD, Title TBD 16 CESCB Chalk Talk, Noon, 3070 HLSIC, Patrick E. Fields, PhD, Title TBD

17 Seminar, 8:30 - 9:30 a.m., Lied Aud., Julie Kim, PhD, Northwestern University, Influence of AKT on Progesterone Receptor Function, Host: Warren B. Nothnick 21 Histone-Chromatin Interest Group Meeting, 4-5 p.m., 1001-1003 Beller Conference Center; Udayan Apte, PhD, presenting (title TBD)

23 CESCB Chalk Talk, Noon, 3070 HLSIC, Luciano DiTacchio, Title TBD

30 * CDOHAD Chalk Talk, Noon, 3070 HLSIC, Kathleen Gustafson, PhD, Title TBD

May 2014

7 * CDOHAD Chalk Talk, Noon, 3070 HLSIC, Yafeng Dong, PhD, Title TDB

8 Seminar, 8:30-9:30 a.m., Lied Aud., Tracy L. Bale, PhD, University of Pennsylvania, Stressed Parents: Maternal and Paternal Epigenetic Reprogramming of the Developing Brain, Host Julie A. Carlsten Christianson

14 * CESCB Chalk Talk, Noon, 3070 HLSIC, Adam Krieg, PhD, Title TBD

15 Seminar, 8:30-9:30 a.m., Lied Aud., Frank McKeon, PhD, The Jackson Laboratory, Adult Stem Cells in Regenerative Medicine and Human Disease, Host: Fariba Behbod

22 * CESCB Chalk Talk, Noon, 3070 HLSIC, Joseph Fontes, PhD, Title TBD 29 * CESCB Chalk Talk, Noon, 3070 HLSIC, Ann Manzardo, PhD, Title TBD *IRHRM Pilot Award Recipient Progress Report

Sculpture: “Stemmer No. 7”, by David Fried, 2005

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