DEPARTMENT OF EXPERIMENTAL AND CLINICAL …DEPARTMENT OF EXPERIMENTAL AND CLINICAL PHARMACOLOGY Contents 2 Letter from the Department Head 4 Department Members 6 Research 20 Teaching

2014 Annual Report

DEPARTMENT OF EXPERIMENTAL AND CLINICAL PHARMACOLOGY

DEPARTMENT OF EXPERIMENTAL AND CLINICAL PHARMACOLOGY

Contents

2 Letter from the Department Head

4 Department Members

6 Research

20 Teaching

21 Service

22 Graduate Program

2014 Annual Report

©2015 Regents of the University of Minnesota.

The University’s mission, carried out on multiple campuses and throughout the state, is threefold: research and discovery, teaching and learning, and outreach and public service. The University of Minnesota shall provide equal access to and opportunity in its programs, facilities, and employment without regard to race, color, creed, religion, national origin, gender, age, marital status, disability, public assistance status, veteran status, sexual orientation, gender identity, or gender expression.

This publication is available in alternative formats upon request. Direct requests to Erin McGonagle, Department of Experimental and Clinical Pharmacology, mcgo��@umn.edu, 612-624-7639.

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DEAR COLLEAGUES AND FRIENDS,

FRO

M T

HE

DE

PAR

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NT

HE

AD

The mission of

the Department

of Experimental

and Clinical

Pharmacology

is to discover,

disseminate,

and apply new

knowledge

related to safe,

effective, and

economical

medication use

in patients.

The success of a department depends upon its mem-bers: their innovative and rigorous research, their leadership and service within the profession, the passion and excellence they bring to training the next

generation of thinkers and practitioners. I am proud to say that the Department of Experimental and Clinical Pharmacology (ECP) com-prises many such renowned investigators and scholars. The decades of scholarship of our professors, the fresh perspectives of our junior faculty, along with the proven excellence of our research and adminis-trative staff, all contribute to our department’s standing as one of the top programs of its kind in the nation.

In the past year, new sponsored projects by faculty researchers were begun in areas as diverse as Alzheimer’s disease, Parkinson’s disease, and tobacco dependence, to name but a few. ECP faculty have also taken on a leadership role in helping advance the University’s efforts in the area of Precision Medicine and Health.

In order to strategically build upon the existing expertise of our renowned faculty, the department proudly welcomed two new mem-bers in August 2014 after an extensive national search. Dr. Melanie Nicol, who specializes in drug therapy issues of patients receiving HIV medications, joined us as a tenure-track assistant professor. Dr. Jeffrey Bishop joined us as a tenured associate professor specializing in the pharmacogenetics of psychotherapeutic agents; he will also contribute to ongoing and new initiatives related to precision medicine.

We congratulate ECP faculty member and director of graduate stud-ies Angela K. Birnbaum, who was promoted this past year from associ-ate professor to professor (with tenure). Dr. Birnbaum has also shep-herded the rollout of a new research emphasis track for professional students who seek a structured approach to becoming more involved in translational research.

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Robert J. Straka, Pharm.D.Professor and Department Head

Teaching and training the next generation of clinical scientists and scholars continues to be a significant part of ECP’s role within the College. The second year of our new curriculum for Pharm.D. students commenced, and our faculty worked tirelessly to ensure the outstanding educational experience for which the College of Pharmacy has become known.

In 2014, students within our distinguished ECP graduate pro-gram, which trains future leaders of clinical and translational research within human pharmacology and therapeutics, present-ed research abstracts at national conferences, had publications accepted in peer-reviewed journals, and won competitive fellow-ships to support their graduate research. ECP also continues to actively build a strategic alignment with the University’s Clinical and Translational Science Institute and has an impressive record of being awarded their competitive summer research scholarships for students in the professional and graduate programs.

I am pleased to present you with this 2014 Annual Report. More of our department successes from the last year are cataloged in the pages that follow. I invite you to read through the diverse ar-ray of accomplishments that establish our department as a leading group of translational scientists in the discipline of experimental and clinical pharmacology.

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Angela K. Birnbaum, Ph.D.Professor; Director of Graduate Studies

Jeffrey Bishop, Pharm.D., M.S.Associate Professor

Richard C. Brundage, Ph.D., Pharm.D.

Professor

Scott A. Chapman, Pharm.D.Associate Professor

James C. Cloyd, Pharm.D.Professor; Weaver Endowed Chair in Orphan Drug Development

Jeannine M. Conway, Pharm.D.Assistant Professor; Director of Applied Learning

Esam El-Fakahany, Ph.D.Professor; Associate Dean for Research and Graduate Studies

Cynthia R. Gross, Ph.D.Professor

David R. Guay, Pharm.D.Professor Emeritus

Pamala A. Jacobson, Pharm.D.Professor

L’Aurelle A. Johnson, Ph.D.Assistant Professor

Mark N. Kirstein, Pharm.D.Associate Professor

Michael Kotlyar, Pharm.D.Associate Professor

Ilo E. Leppik, M.D.Professor

Ling Li, Ph.D.Professor; VFW Endowed Chair in Geriatric Pharmacology

Henry J. Mann, Pharm.D.Professor Emeritus

Susan E. Marino, Ph.D.Assistant Professor

Michele Anderson, Ph.D.Research Assistant Professor

Andrew Behm, Pharm.D., CGPAssistant Professor

Greg Beilman, M.D.Professor

Lisa Coles, Ph.D.Research Assistant Professor

Kristin Engebretsen, Pharm.D.Professor

Dean T. Filandrinos, Pharm.D.Assistant Professor

Mary E. Foss, Pharm.D.Assistant Professor

John F. Gualtieri, Pharm.D.Assistant Professor

Serge Guzy, Ph.D.Professor

Nitin Kaila, Ph.D.Assistant Professor

FACULTY

Reena Kartha, Ph.D.Research Assistant Professor

Daniel E. Keyler, Pharm.D.Professor

Frank N. Konstantinides, M.T., M.S.Professor

Robert Kriel, M.D.Research Professor

Smita Kshirsagar, Ph.D.Instructor

Marie D. Kuker, R.Ph.Assistant Professor

Stephen H. LeMaster, Pharm.D.Assistant Professor

Len Lichtblau, Ph.D.Associate Professor

Ramaiah Muthyala, Ph.D. Associate Professor

Patrick J. Parks, M.D., Ph.D.Associate Professor

David Parra, Pharm.D.Associate Professor

Pamela A. Pawloski, Pharm.D.Assistant Professor

Kelly M. Sioris, Pharm.D.Assistant Professor

Catherine St. Hill, D.V.M., Ph.D.Assistant Professor

John V. St. Peter, Pharm.D.Associate Professor

Jeanine Utz, Pharm.D.Assistant Professor

Chester B. Whitley, M.D., Ph.D.Professor

Rank and appointment as of 12/31/2014.

ADJUNCT FACULTY

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Melanie R. Nicol, Ph.D.Assistant Professor

William S. Oetting, Ph.D.Professor

Marnie L. Peterson, Ph.D., Pharm.D.Associate Professor; Associate Director of Graduate Studies

John C. Rotschafer, Pharm.D.Professor

Shellina Scheiner, Pharm.D.Assistant Professor

Leo J. Sioris, Pharm.D.Professor

Debra J. Skaar, Pharm.D.Associate Professor

Robert J. Straka, Pharm.D.Professor; Department Head

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Research and Administrative StaffMichele Anderson, Ph.D. ................................................................Senior Research Associate, Peterson Research ProgramLaura Breshears, Ph.D. ....................................................................Research Associate, Peterson Research ProgramMarcia Brott .....................................................................................Assistant Scientist, Oetting Research ProgramRebecca Brown ................................................................................Study Coordinator, Jacobson Research ProgramCarol Ann Dickinson ......................................................................Associate AdministratorSheena Dufresne ..............................................................................Study Coordinator, Kotlyar Research ProgramJames Fisher .....................................................................................Technical Director, CPAS LaboratoryKathy Fox .........................................................................................Study Coordinator, Birnbaum Research ProgramLaurie Baeker Hovde .......................................................................Coordinator, MTRF LaboratoriesDede Johnston .................................................................................Associate AdministratorReena Kartha, Ph.D.........................................................................Research Associate, Center for Orphan Drug ResearchFrank N. Konstantinides, M.T., M.S. ............................................Director, CPAS LaboratoryKyle LeBlanc ....................................................................................Junior Scientist, Li Research ProgramErin McGonagle ..............................................................................Program/Project SpecialistAnnie Mills .......................................................................................Study Coordinator, Kotlyar Research ProgramUsha Mishra .....................................................................................Assistant Scientist, Center for Orphan Drug ResearchJohn O. Rarick .................................................................................Study Coordinator, Birnbaum Research ProgramMichaela Roslawski .........................................................................Junior Scientist, Birnbaum Research ProgramBrent Williams .................................................................................Scientist, CPAS Laboratory

New Graduate Students—Fall 2014Samuel P. Callisto .............................................................................Advisor: Susan E. Marino, Ph.D.Natalie S. Schmitz ...........................................................................Advisor: James C. Cloyd, Pharm.D.

Continuing Graduate Students—Fall 2014Mariam Ahmed, B.S. .......................................................................Advisor: Richard C. Brundage, Ph.D., Pharm.D.Ali Alhadab, Pharm.D. ....................................................................Advisor: Richard C. Brundage, Ph.D., Pharm.D. Co-Advisor: Marnie L. Peterson, Ph.D., Pharm.D. Caroline Churchill, B.S. ..................................................................Advisor: Carolyn Fairbanks, Ph.D.Taraswi Mitra Ghosh, M.Sc. ...........................................................Advisor: Jatinder Lamba, Ph.D. Aaron Gillman, B.S. .........................................................................Advisor: Marnie L. Peterson, Ph.D., Pharm.D.Mary Holmay, R.N. .........................................................................Advisor: James C. Cloyd, Pharm.D.David Hottman, B.S. .......................................................................Advisor: Ling Li, Ph.D.Krista Johnson, B.S. .........................................................................Advisor: James C. Cloyd, Pharm.D. Chay Ngee Lim, B.Sc.......................................................................Advisor: Angela K. Birnbaum, Ph.D.Malek Okour, B.S. ............................................................................Advisor: Richard C. Brundage, Ph.D., Pharm.D.Cristina Peterson, B.S......................................................................Advisor: Carolyn Fairbanks, Ph.D. Youssef Roman, Pharm.D. ..............................................................Advisor: Robert J. Straka, Pharm.D. Kinjal Sanghavi, B.Pharm. ..............................................................Advisor: Pamala A. Jacobson, Pharm.D.Harrison Tam, B.S. ...........................................................................Advisor: L’Aurelle A. Johnson, Ph.D.

New and Continuing Post-Docs, Fellows, and ResidentsSai Praneeth Reddy Bathena, Ph.D. ...............................................Advisor: Angela K. Birnbaum, Ph.D. Laura Breshears, Ph.D. ....................................................................Advisor: Marnie L. Peterson, Ph.D., Pharm.D.Shaowu Cheng, Ph.D. ......................................................................Advisor: Ling Li, Ph.D.Shuang Liang, Ph.D. ........................................................................Advisor: Mark N. Kirstein, Pharm.D.Joseph Schneider, Pharm.D. ...........................................................Advisor: James C. Cloyd, Pharm.D.

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RESEARCH

Groundbreaking and critical research is conducted in the Department of

Experimental and Clinical Pharmacology. Faculty research programs focus on

oncology, transplantation, infectious diseases, genomics, geriatrics, critical

care, neuroscience, cardiovascular diseases, pediatrics, integrative therapies

and outcomes, and psychiatry. ECP is home to the Lawrence C. Weaver

Endowed Chair in Orphan Drug Development and the VFW Endowed Chair

in Geriatric Pharmacotherapy. In addition, ECP’s state-of-the-art, CLIA-

certified Clinical Pharmacology Analytical Services Laboratory has provided

an important research resource to both University researchers and external

customers for ten years.

Our 23 regular faculty members routinely present important research findings

at national and international conferences, lecture and collaborate across the

country, serve as reviewers and editorial board members of international

journals, hold leadership positions in national organizations, and serve on

National Institutes of Health and other granting agencies’ review committees.

RE

SEA

RC

H

In 2014:

• New grants received by ECP faculty = 22

• Peer-reviewed articles published by ECP faculty = 62

• Books and chapters published by ECP faculty = 4

• Department expenditures on sponsored projects (exclusive of salaries/

fringe) = $1,919,492

• Department salaries/fringe offset by sponsored projects = $1,745,449

• Percentage of ECP faculty salaries generated by sponsored projects in FY

2014 (July 1, 2013 to June 30, 2014) = 19.2%

ECP Department

faculty conduct

groundbreaking

research in areas

such as oncology,

transplantation,

infectious diseases,

pharmacogenomics,

orphan drugs,

cardiovascular

diseases, Alzheimer’s,

and critical care.

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New Sponsored Projects by ECP Faculty in 2014

Faculty Project Description Sponsor

James C. Cloyd (PI) Prodrug/Enzyme Combinations for Rapid Nasal Absorption of Benzodiazepines

American Epilepsy Society

James C. Cloyd (Co-I) Canine Epilepsy: Genetic Variants, Biomarkers, and New Therapies

American Kennel Club

James C. Cloyd (PI), Ilo E. Leppik (Co-I)

Prodrug/Enzyme Systems for Intranasal Treatment of Seizure Emergencies

Epilepsy Foundation of America

James C. Cloyd (PI) Pharmacotherapy of Inherited Metabolic Disease Pharm.D. Fellowship

Genzyme Corporation

James C. Cloyd (PI) Characterization of Topiramate Disposition in Children using Innovative Analytical Technology

Gillette Children’s Specialty Care

James C. Cloyd (Co-I), Lisa Coles (Co-I)

Use of N-Acetyl Cysteine for the Prevention and Treatment of Hyperglycemia Awareness Autonomic Failure

Juvenile Diabetes Research Foundation

James C. Cloyd (Co-PI) Lysosomal Disease Network NIH National Institute of Neurological Disorders and Stroke

• Center for Clinical and Cognitive Neuropharmacology (Dr. Susan Marino)

• Center for Excellence in Critical Care (Dr. Greg Beilman)

• Center for Forecasting Drug Response

• Center for Orphan Drug Research (Dr. Jim Cloyd)

• Pathway-Driven Pharmacogenomics U of M Alliance – Institute for Personalized Medicine

(Dr. Pamala Jacobson)

Research Centers within ECP

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James C. Cloyd (PI) Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease: Potential Use of Antioxidant/Anti-Inflammatory Medications

NIH National Institute of Neurological Disorders and Stroke

James C. Cloyd (Co-I) Oral NAC for Parkinson’s Disease: Repeated Dose Pharmacokinetics and Pharmacodynamics

Parkinson’s UK

Jeannine M. Conway (PI) A Community Pharmacy Coordinated Program to Enhance Control of High Blood Pressure and Diabetes in a Suburban Minnesota Community

Centers for Disease Control/MN Department of Health

Mark N. Kirstein (PI) Optimization of Imprime PGG Effect on Antitumor Activity of Tumor Targeting Monoclonal Antibody inSyngeneic/Xenogeneic Tumor Mouse Model

Biothera

Michael Kotlyar (PI) Effect of Banning Menthol Flavored Cigarettes on Smoking Cessation

Clearway MN

Robert Kriel (PI) Development of Intravenous Baclofen Allaysis

Robert Kriel (PI), James C. Cloyd (Co-I), Lisa Coles (Co-I)

Prevention of Baclofen Withdrawal Syndrome: Two-Way Crossover Study

Paralyzed Veterans of America

Susan E. Marino (PI) Assay Validation of Vinpocetine and Apovincaminic Acid by LC-MS

Stanford University

Marnie L. Peterson (PI) Mucosal Biofilm Infection Model of Methicillin Resistant Staphylococcus aureus for Screening of NovelAnti-Biofilm Agents/Formulations

CSA Biotech

John Rotschafer (PI) Infectious Diseases Pharmacy Fellowship Forum 2015 Cubist Pharmaceuticals, Inc.

New Sponsored Projects by ECP Faculty in 2014, continued

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Ongoing Sponsored Projects by ECP Faculty in 2014


Angela K. Birnbaum (Co-PI), Jatinder Lamba (Co-PI)

Pharmacogenomics and Pharmacokinetics of Lamotrigine in Early Pregnancy

Epilepsy Foundation of America, Inc.

Angela K. Birnbaum (Co-I) Preclinical Studies of a Heroin/Morphine Vaccine for Opiate Addiction

NIH National Institute on Drug Abuse

Angela K. Birnbaum (PI) Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs – Pharmacokinetics Laboratory Core

NIH National Institute of Neurological Disorders and Stroke

New Intramural Projects by ECP Faculty in 2014


James C. Cloyd (PI) Acquisition of a Triple Quad LC-MS System for Translational Research on Orphan Drugs

U of M Grant-in-Aid of Research, Artistry & Scholarship Program

Michael Kotlyar (PI) Novel Medication as a Potential Smoking Cessation Aid AHC Faculty Research Development Program

Ling Li (PI) Role of C-Reactive Protein in Alzheimer’s Disease AHC Faculty Research Development Program

Marnie L. Peterson (PI) The Role of the Vaginal Microbiota in Sexually Transmitted Infections (STI)

U of M Grant-in-Aid of Research, Artistry & Scholarship Program

Robert Straka (PI) Genomics of Hyperuricemia Therapy in Hmong CTSI Community Health Collaborative Grants Program

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Angela K. Birnbaum (PI) Pharsight–University of Minnesota Pharmacometrics Collaboration

Pharsight Corporation

Richard C. Brundage (Co-I) University of Minnesota Clinical and Translational Science Institute

NIH National Center for Research Resources

Richard C. Brundage (PI) Pharmacogenetics and Drug Interactions NIH National Institute of General Medical Sciences

Richard C. Brundage (PI) Novartis Pharmacometrics Traineeship Novartis Pharma AG

Richard C. Brundage (PI) Pfizer Pharmacometrics Traineeship Pfizer, Inc.


Identifying New Therapies for Infantile Spasms Cure Foundation/Department of Defense

James C. Cloyd (PI) Clinical Pharmacotherapy and Pharmacogenetics of Inherited Metabolic Diseases

Genzyme Corporation

James C. Cloyd (PI), Lisa Coles (Co-I)

Differential Pharmacological Effect of Ezogabine on Canine EEG

GlaxoSmithKline


Prevention of Baclofen Withdrawal Syndrome: Two-Way Crossover Study

Medtronic, Inc.

James C. Cloyd (Co-I), Reena Kartha (Co-I)

Phase II Clinical Trial to Evaluate the Benefits of Post-Conditioning in STEMI

NIH National Heart, Lung, and Blood Institute

Esam E. El-Fakahany (Co-I) Leveraging Best Practices in Mentoring from the Collective Experience of CNPCs

NIH National Institute on Minority Health and Health Disparities

Cynthia R. Gross (PI) Mindfulness for Symptom Reduction: A Transplant Candidate Study (a project within the program grant Studies of Organ Transplantation in Animals and Man)

NIH National Institute of Diabetes and Digestive and Kidney Diseases

Ongoing Sponsored Projects by ECP Faculty in 2014, continued

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Pamala A. Jacobson (Co-I), Mark N. Kirstein (Co-I)

Cancer Center Support Grant NIH National Cancer Institute

Pamala A. Jacobson (Co-I), William S. Oetting (Co-I)

Genomics of Kidney Transplantation NIH National Institute of Allergy and Infectious Diseases

Mark N. Kirstein (PI) Vitamin D3 Effects on Musculoskeletal Symptoms with Use of Aromatase Inhibitors

Park Nicollet Institute

Michael Kotlyar (PI) Smoker Response to Banning of Menthol-Flavored Cigarettes

Clearway MN

Michael Kotlyar (Co-I) Evaluating New Nicotine Standards for Cigarettes NIH National Institute on Drug Abuse

Michael Kotlyar (PI) Medicinal Nicotine for Preventing Stress-Induced Craving and Withdrawal Symptoms

NIH National Institute on Drug Abuse

Michael Kotlyar (PI) GRAND 2012: Use of Medicinal Nicotine for Preventing Cue-Induced Craving and Withdrawal Symptoms

Pfizer, Inc.

Ilo E. Leppik (Co-I) Leveraging the EHR to Collect and Analyze Social, Behavioral & Family Factors

NIH National Library of Medicine

Ilo E. Leppik (PI) An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects with Seizure Clusters

PharmaNet, Inc.

Ilo E. Leppik (PI) A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects with Seizure Clusters

PharmaNet, Inc.

Ling Li (PI) ApoJ/Clusterin Peptide as a Novel Therapeutic Agent for Alzheimer's Disease

Alzheimer's Drug Discovery Foundation

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Ling Li (PI) Protective Mechanisms of Statins in Alzheimer’s Disease NIH National Institute on Aging

Susan E. Marino (PI), Angela K. Birnbaum (Co-I), Pamala A. Jacobson (Co-I)

Cognitive and Motor Effects of Treatment with a Calcineurin Inhibitor (Tacrolimus) versus Belatacept in Kidney Transplant Patients

Bristol-Myers Squibb Com-pany

Susan E. Marino (PI) Professional Fighters Brain Health Study The Cleveland Clinic

Susan E. Marino (PI), Angela K. Birnbaum (Co-I), Ilo E. Leppik (Co-I)

Characterizing and Predicting Drug Effects on Cognition NIH National Institute of Neurological Disorders and Stroke

Marnie L. Peterson (Co-I) Immunological Factors and Risk of Vulvodynia NIH National Institute of Child Health and Human Development

Marnie L. Peterson (PI) Mucosal Models of Infection for Antisepsis 3M

Marnie L. Peterson (PI) Mucosal Models for Skin and Wound Infections 3M

Shellina R. Scheiner (Co-I) Minnesota Area Geriatric Education Center US Department of Health and Human Services HRSA

Debra J. Skaar (Co-I) Testing the Feasibility of Patient-Controlled Sedation in Ventilated ICU Patients

NIH National Institute of Nursing

Jeanine Utz (PI) Placebo Controlled Trial Evaluating Gabapentin for the Treatment of Small Fiber Neuropathic Pain in Patients with Fabry Disease

Genzyme Corporation


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Reena Kartha (Co-I) Determination of Endogenous Levels of Nitric Oxide and Hydrogen Sulfide sin Patients with Obstructive Sleep Apnea

University of Minnesota Foundation

Mark N. Kirstein (Co-I) Pilot Analysis of Unbound Sorafenib: Relevance to Efficacy and Toxicity in a Phase I Trial and to In-vitro Cytotoxicity

University of Minnesota Foundation

Ling Li (PI) Therapeutic Potential of a Novel Neuroprotective Agent for Alzheimer's Disease

Engebretson/Bighley Drug Design & Development Grant

Marnie L. Peterson (PI) Alpha Toxin: Role in Biofilm Formation by MRSA Wound Isolates and Therapeutic Target

CTSI-Ed R-to-R Scholars Program Grant

Marnie L. Peterson (PI) Development of a Biotherapeutic for Prophylaxis and Treatment of S. aureus Disease

Engebretson/Bighley Drug Design & Development Grant

Robert J. Straka (PI) Pharmacogenomic Markers of Lipid Response to Fenofibrate in a Hispanic Population

Institute of Human Genetics

Ongoing Intramural Projects by ECP Faculty in 2014

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Polepally AR, Pennell PB, Brundage RC, Stowe ZN, Newport DJ, Viguera AC, Ritchie JC, Birnbaum AK. Model-based lamotrigine clearance changes during pregnancy: clinical implication. Ann Clin Transl Neurol. 2014 Feb;1(2):99-106. PMID: 24883336 PMCID: PMC4038031

Ahmed GF, Marino SE, Brundage RC, Pakhomov SV, Leppik IE, Cloyd JC, Clark A, Birnbaum AK. Pharmacoki-netic-pharmacodynamic (PK-PD) modeling of intravenous and oral topiramate and its effect on phonemic fluency in adult human volunteers. Br J Clin Pharmacol. 2014 Nov 18. doi: 10.1111/bcp.12556. [Epub ahead of print] PMID: 25403343

Sarapas C, Katz AC, Nelson BD, Campbell ML, Bishop JR, Robison-Andrew EJ, Altman SE, Gorka SM, Shankman SA. Are individual differences in appetitive and defensive motivation related? A psychophysiological examination in two samples. Cogn Emot. 2014;28(4):636-55. Epub 2013 Nov 6. PMID: 24191979 PMCID: PMC3962705

Drozda K, Müller DJ, Bishop JR. Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options. Pharmacotherapy. 2014 Feb;34(2):166-84. PMID: 24523097 PMCID: PMC3939793

Stein MA, Waldman I, Newcorn J, Bishop J, Kittles R, Cook EH Jr. Dopamine transporter genotype and stimulant dose-re-sponse in youth with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2014 Jun;24(5):238-44. Epub 2014 May 9. PMID: 24813374 PMCID: PMC4064733

Lencer R, Bishop JR, Harris MS, Reilly JL, Patel S, Kittles R, Prasad KM, Nimgaonkar VL, Keshavan MS, Sweeney JA. Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis. Eur Arch Psychiatry Clin Neurosci. 2014 Jun;264(4):345-55. Epub 2013 Oct 25. PMID: 24682224 PMCID: PMC4290665

Nelson BD, Bishop JR, Sarapas C, Kittles RA, Shankman SA. Asians demonstrate reduced sensitivity to unpredictable threat: a preliminary startle investigation using genetic ancestry in a multiethnic sample. Emotion. 2014 Jun;14(3):615-23. Epub 2014 Apr 7. PMID: 24708496 PMCID: PMC4049523

Katz AC, Sarapas C, Bishop JR, Patel SR, Shankman SA. The mediating effect of prefrontal asymmetry on the relationship between the COMT Val158Met SNP and trait consummatory positive affect. Cogn Emot. 2014 Sep 8:1-15. [Epub ahead of print] PMID: 25195915

Keedy SK, Bishop JR, Weiden PJ, Sweeney JA, Rosen C, Marvin R, Reilly JL. Disease and drug effects on internally-gen-erated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder. Schizophr Res. 2014 Oct;159(1):101-6. Epub 2014 Aug 8. PMID: 25112158 PMCID: PMC4177289

Rubin LH, Carter CS, Bishop JR, Pournajafi-Nazarloo H, Drogos LL, Hill SK, Ruocco AC, Keedy SK, Reilly JL, Keshavan MS, Pearlson GD, Tamminga CA, Gershon ES, Sweeney JA. Reduced levels of vasopressin and reduced behavioral modula-tion of oxytocin in psychotic disorders. Schizophr Bull. 2014 Nov;40(6):1374-84. Epub 2014 Mar 11. PMID: 24619535 PMCID: PMC4193712

DiDomenico RJ, Bress AP, Na-Thalang K, Tsao YY, Groo VL, Deyo KL, Patel SR, Bishop JR, Bauman JL. Use of a simpli-fied nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Pharmacothera-py. 2014 Nov;34(11):1121-31. Epub 2014 Aug 28. PMID: 25164709 PMCID: PMC4227958

Published Articles by ECP Faculty in 2014

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Stevenson JM, Bishop JR. Genetic determinants of selective serotonin reuptake inhibitor related sexual dysfunction. Phar-macogenomics. 2014 Nov;15(14):1791-1806. PMID: 25493571

Chen C, Zhang C, Cheng L, Reilly JL, Bishop JR, Sweeney JA, Chen HY, Gershon ES, Liu C. Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia. Bipolar Disord. 2014 Dec;16(8):790-9. Epub 2014 Sep 22. PMID: 25243493 PMCID: PMC4302408

Bishop JR, Reilly JL, Harris MS, Patel SR, Kittles R, Badner JA, Prasad KM, Nimgaonkar VL, Keshavan MS, Sweeney JA. Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia. Psychopharmacology (Berl). 2015 Jan;232(1):145-54. Epub 2014 Aug 7. PMID: 25096017 PMCID: PMC4282597

Giakoumatos CI, Nanda P, Mathew IT, Tandon N, Shah J, Bishop JR, Clementz BA, Pearlson GD, Sweeney JA, Tamminga CA, Keshavan MS. Effects of lithium on cortical thickness and hippocampal subfield volumes in psychotic bipolar disorder. J Psychiatr Res. 2015 Feb;61:180-7. Epub 2014 Dec 23. PMID: 25563516

Salem AH, Fletcher CV, Brundage RC. Pharmacometric characterization of efavirenz developmental pharmacokinetics and pharmacogenetics in HIV-infected children. Antimicrob Agents Chemother. 2014;58(1):136-43. Epub 2013 Oct 21. PMID: 24145522 PMCID: PMC3910794

Wang T, Baron K, Zhong W, Brundage R, Elmquist W. Bayesian approach to estimate AUC, partition coefficient and drug targeting index for studies with serial sacrifice design. Pharm Res. 2014 Mar;31(3):649-59. doi: 10.1007/s11095-013-1187-0. Epub 2013 Oct 3. PMID: 24092052 PMCID: PMC3943927

Vezina HE, Brundage RC, Balfour HH Jr. Population pharmacokinetics of valganciclovir prophylaxis in paediatric and adult solid organ transplant recipients. Br J Clin Pharmacol. 2014 Aug;78(2):343-52. PMID: 24528138 PMCID: PMC4137826

Bart G, Lenz S, Straka RJ, Brundage RC. Ethnic and genetic factors in methadone pharmacokinetics: a population phar-macokinetic study. Drug Alcohol Depend. 2014 Dec 1;145:185-93. Epub 2014 Oct 24. PMID: 25456329 PMCID: PMC4254688

Chapman SA, Irwin ED, Abou-Karam NM, Rupnow NM, Hutson KE, Vespa J, Roach RM. Comparison of 3-factor pro-thrombin complex concentrate and low-dose recombinant factor VIIa for warfarin reversal. World J Emerg Surg. 2014 Apr 15;9:27. doi: 10.1186/1749-7922-9-27. eCollection 2014. PMID: 24731393 PMCID: PMC3996494

Clark AM, Halvorsen MB, Braun TL, Johnson KM, Cloyd JC. USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. Epilepsia. 2014 Jul;55(7):1069-76. Epub 2014 May 23. PMID: 24861853 PMCID: PMC4283972

Scherkenbach LA, Coles LD, Patterson EE, Cloyd JC, Krach LE, Kriel RL. Pharmacokinetics and pharmacodynamics of in-travenous baclofen in dogs: a preliminary study. J Pharm Pharmacol. 2014 Jul;66(7):935-42. Epub 2014 Feb 13. PMID: 24697865

Agarwal SK, Kriel RL, Cloyd JC, Coles LD, Scherkenbach LA, Tobin MH, Krach LE. A pilot study assessing pharmacoki-netics and tolerability of oral and intravenous baclofen in healthy adult volunteers. J Child Neurol. 2015 Jan;30(1):37-41. Epub 2014 Jul 14. PMID: 25028414

Published Articles by ECP Faculty in 2014, continued

16

Conway JM, Brown MC. A flowchart for selecting an ointment base. Am J Pharm Educ. 2014 Feb 12;78(1):16. doi: 10.5688/ajpe78116. PMID: 24558284 PMCID: PMC3930240

Conway JM, Birnbaum AK, Leppik IE, Pennell PB, White JR, Rarick JO, Remmel RP. Safety of an intravenous formu-lation of lamotrigine. Seizure. 2014 May;23(5):390-2. doi: 10.1016/j.seizure.2014.01.019. Epub 2014 Jan 31. PMID: 24560492 PMCID: PMC4023538

Jakubík J, Šantrůčková E, Randáková A, Janíčková H, Zimčík P, Rudajev V, Michal P, El-Fakahany EE, Doležal V. Outline of therapeutic interventions with muscarinic receptor-mediated transmission. Physiol Res. 2014;63 Suppl 1:S177-89. PMID: 24564657

Šantrůčková E, Doležal V, El-Fakahany EE, Jakubík J. Long-term activation upon brief exposure to xanomeline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors. PLoS One. 2014 Feb 18;9(2):e88910. doi: 10.1371/journal.pone.0088910. eCollection 2014. PMID: 24558448 PMCID: PMC3928307

Michal P, El-Fakahany EE, Doležal V. Changes in membrane cholesterol differentially influence preferential and non-pref-erential signaling of the M1 and M3 muscarinic acetylcholine receptors. Neurochem Res. 2014 May 13. [Epub ahead of print] PMID: 24821386

Jakubík J, Zimčík P, Randáková A, Fuksová K, El-Fakahany EE, Doležal V. Molecular mechanisms of methoctramine bind-ing and selectivity at muscarinic acetylcholine receptors. Mol Pharmacol. 2014 Aug;86(2):180-92. doi: 10.1124/mol.114.093310. Epub 2014 May 28. PMID: 24870405

Hubbling A, Reilly-Spong M, Kreitzer MJ, Gross CR. How mindfulness changed my sleep: focus groups with chronic in-somnia patients. BMC Complement Altern Med. 2014 Feb 10;14:50. PMID: 24512477 PMCID: PMC3927626

Talley KM, Wyman JF, Gross CR, Lindquist RA, Gaugler JE. Change in balance confidence and its associations with in-creasing disability in older community-dwelling women at risk for falling. J Aging Health. 2014 Mar 25;26(4):616-636. [Epub ahead of print]

Anderson LH, Whitebird RR, Schultz J, McEvoy CE, Kreitzer MJ, Gross CR. Healthcare utilization and costs in persons with insomnia in a managed care population. Am J Manag Care. 2014 May;20(5):e157-65. PMID: 25326930

Zargarian N, Lindquist R, Gross CR, Treat-Jacobson D. Outcome measures of behavioral weight loss programs in perimeno-pause. South Med J. 2014 Aug;107(8):486-96. PMID:25084185

Messersmith EE, Gross CR, Beil CA, Gillespie BW, Jacobs C, Taler SJ, Merion RM, Jowsey SG, Leichtman AB, Hong BA; the RELIVE Study Group. Satisfaction with life among living kidney donors: a RELIVE study of long-term donor outcomes. Transplantation. 2014 Aug 18. [Epub ahead of print] PMID: 25136843

Weber M, Faravardeh A, Jackson S, Berglund D, Spong R, Matas AJ, Gross CR, Ibrahim HN. Quality of life in elderly kid-ney transplant recipients. J Am Geriatr Soc. 2014 Oct;62(10):1877-82. Epub 2014 Oct 3. PMID: 25284598


17

Jowsey SG, Jacobs C, Gross CR, Hong BA, Messersmith EE, Gillespie BW, Beebe TJ, Kew C, Matas A, Yusen RD, Hill-Cal-lahan M, Odim J, Taler SJ; RELIVE Study Group. Emotional well-being of living kidney donors: findings from the RELIVE Study. Am J Transplant. 2014 Nov;14(11):2535-44. Epub 2014 Oct 7. PMID: 25293374 PMCID: PMC4205186

McCune J, Jacobson P, Wiseman A, Militano O. Optimizing drug therapy in pediatric SCT: focus on pharmacokinetics. Bone Marrow Transplantation. 2014 Oct 27. [Epub ahead of print] doi:10.1038/bmt.2014.235.

Tam HK, Kelly AS, Metzig AM, Steinberger J, Johnson LA. Xanthine oxidase and cardiovascular risk in obese children. Child Obes. 2014 Apr;10(2):175-80. doi: 10.1089/chi.2013.0098. Epub 2014 Feb 25. PMID: 24568669 PMCID: PMC3992000

Khatri A, Williams BW, Fisher J, Brundage RC, Gurvich VJ, Lis LG, Skubitz KM, Dudek AZ, Greeno EW, Kratzke RA, Lamba JK, Kirstein MN. SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours. Br J Cancer. 2014 Jan 21;110(2):304-12. Epub 2013 Dec 3. PMID:24300978

Leppik IE, Birnbaum AK. Treating epilepsy in the elderly: more an art than science. Cleve Clin J Med. 2014 Aug;81(8):499-500. doi: 10.3949/ccjm.81a.14030. PMID: 25085988

Wood WG, Li L, Müller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer’s disease: a debatable hypothesis. J Neurochem. 2014 May;129(4):559-72. doi: 10.1111/jnc.12637. Epub 2014 Jan 2. PMID: 24329875 PMCID: PMC3999290

Parent MA, Hottman DA, Cheng S, Zhang W, McMahon LL, Yuan LL, Li L. Simvastatin treatment enhances NMDAR-me-diated synaptic transmission by upregulating the surface distribution of the GluN2B subunit. Cell Mol Neurobiol. 2014 Jul;34(5):693-705. doi: 10.1007/s10571-014-0051-z. Epub 2014 Apr 1. PMID: 24687455 PMCID: PMC4142643

Hottman DA, Li L. Protein prenylation and synaptic plasticity: implications for Alzheimer’s disease. Mol Neurobiol. 2014 Aug;50(1):177-85. doi: 10.1007/s12035-013-8627-z. Epub 2014 Jan 5. PMID: 24390573 PMCID: PMC4082763

Cheng S, LeBlanc KJ, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alz-heimer’s disease. PLoS One. 2014 Oct 2;9(9):e108845. doi: 10.1371/journal.pone.0108845. eCollection 2014. PMID: 25275487 PMCID: PMC4183525

Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and cognition in neurodegenerative disorders. Neurobiol Dis. 2014 Dec;72 Pt A:22-36. doi: 10.1016/j.nbd.2014.07.015. Epub 2014 Aug 13. PMID: 25131449 PMCID: PMC4252583

Chen Y, Peng Y, Che P, Gannon M, Liu Y, Li L, Bu G, van Groen T, Jiao K, Wang Q. α(2A) adrenergic receptor promotes am-yloidogenesis through disrupting APP-SorLA interaction. Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17296-301. doi: 10.1073/pnas.1409513111. Epub 2014 Nov 17. PMID: 25404298 PMCID: PMC4260556

Marino SE, Birnbaum AK, Pakhomov S. Assessing the side effects. International Innovation Healthcare. 2014;162:42-44.

Thompson CG, Sedykh A, Nicol MR, Muratov E, Fourches D, Tropsha A, Kashuba AD. Short communication: cheminfor-matics analysis to identify predictors of antiviral drug penetration into the female genital tract. AIDS Res Hum Retroviruses. 2014 Nov;30(11):1058-64. doi: 10.1089/AID.2013.0254. Epub 2014 Mar 13. PMID: 24512359 PMCID: PMC4208595


18

Oetting WS, Guan W, Schladt DP, Wildebush WA, Becker J, Thyagarajan B, Jacobson PA, Matas AJ, Israni AK. Telomere length of recipients and living kidney donors and chronic graft dysfunction in kidney transplants. Transplantation. 2014 Feb 15;97(3):325-9. doi: 10.1097/01.TP.0000436705.87898.88. PMID: 24492422 PMCID: PMC4104656

Wu J, Lin R, Huang J, Guan W, Oetting WS, Sriramarao P, Blumenthal MN. Functional Fcgamma receptor polymorphisms are associated with human allergy. PLoS One. 2014 Feb 21;9(2):e89196. doi: 10.1371/journal.pone.0089196. eCollection 2014. PMID: 24586589 PMCID: PMC3931680

Stanley CM, Sunyaev SR, Greenblatt MS, Oetting WS. Clinically relevant variants - identifying, collecting, interpreting, and disseminating: the 2013 annual scientific meeting of the Human Genome Variation Society. Hum Mutat. 2014 Apr;35(4):505-10. doi: 10.1002/humu.22516. PMID: 24470180

Irons DE, Iacono WG, Oetting WS, Kirkpatrick RM, Vrieze SI, Miller MB, McGue M. Gamma-aminobutyric acid system genes--no evidence for a role in alcohol use and abuse in a community-based sample. Alcohol Clin Exp Res. 2014 Apr;38(4):938-47. doi: 10.1111/acer.12352. Epub 2014 Jan 24. PMID: 24460875 PMCID: PMC3984361

Vrieze SI, Malone SM, Vaidyanathan U, Kwong A, Kang HM, Zhan X, Flickinger M, Irons D, Jun G, Locke AE, Pistis G, Porcu E, Levy S, Myers RM, Oetting W, McGue M, Abecasis G, Iacono WG. In search of rare variants: preliminary re-sults from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes. Psychophysiology. 2014 Dec;51(12):1309-20. doi: 10.1111/psyp.12350. PMID: 25387710 PMCID: PMC4231480

Muthyala R, Rastogi N, Shin WS, Peterson ML, Sham YY. Cell permeable vanX inhibitors as vancomycin re-sensitizing agents. Bioorg Med Chem Lett. 2014 Jun 1;24(11):2535-8. doi: 10.1016/j.bmcl.2014.03.097. Epub 2014 Apr 8. PMID: 24751446

Spaulding AR, Salgado-Pabón W, Merriman JA, Stach CS, Ji Y, Gillman AN, Peterson ML, Schlievert PM. Vaccination against Staphylococcus aureus pneumonia. J Infect Dis. 2014 Jun 15;209(12):1955-62. doi: 10.1093/infdis/jit823. Epub 2013 Dec 19. PMID: 24357631 PMCID: PMC4038136

Hester EK, McBane SE, Bottorff MB, Carnes TA, Dell K, Gonyeau MJ, Greco AJ, McConnell KJ, Skaar DJ, Splinter MY, Trujillo TC. Educational outcomes necessary to enter pharmacy residency training. Pharmacotherapy. 2014;34(4):e22-5. doi: 10.1002/phar.1411. PMID: 24753155

Knapp KK, Mészáros K, Goldsmith PC, McCarter GC, Hester EK, McBane SE, Bottorff MB, Carnes TA, Dell K, Gonyeau MJ, Greco AJ, McConnell KJ, Skaar DJ, Splinter MY, Trujillo TC. Alternative viewpoint: preparation for residency. Phar-macotherapy. 2014 Aug;34(8):e157-8. doi: 10.1002/phar.1475. PMID: 25112527

Oldenburg NC, Duval S, Luepker RV, Finnegan JR, LaMarre H, Peterson KA, Zantek ND, Jacobs G, Straka RJ, Miller KH, Hirsch AT. A 16-month community-based intervention to increase aspirin use for primary prevention of cardiovascular disease. Prev Chronic Dis. 2014 May 15;11:E83. PMID:24831287 PMCID: PMC4023687

Feitosa MF, Wojczynski MK, Straka R, Kammerer CM, Lee JH, Kraja AT, Christensen K, Newman AB, Province MA, Borecki IB. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol. Front Genet. 2014 Jun 3;5:159. PMID: 24917880 PMCID: PMC4042684


19

Published Books and Chapters by ECP Faculty in 2014

Conway JM, Birnbaum AK. Drugs for epilepsy. In: Whalen K, ed. Lippincott Illustrated Reviews: Pharmacology. 6th ed. Philadelphia, PA: Wolters Kluwer; 2014.

Gross CR, Reibel DK. Mindfulness: a non-pharmacological approach to diabetes management. In: Ie A, Ngnoumen CT, Langer EJ, eds. The Wiley-Blackwell Handbook of Mindfulness. Oxford, UK: Wiley-Blackwell; 2014.

Sanghavi K, Jacobson P. Pharmacogenomics of immunosuppressants. In: Johnson JA, Ellingrod VL, Kroetz DL, Kuo GM, eds. Pharmacogenomics: Applications to Patient Care. 3rd ed. Lenexa, KS: ACCP Publishing; 2015.

Marino GD, Marino SE. Paying homage to the silence of suffering. In: Green RM, Palpant NJ, eds. Suffering and Bioethics. New York, New York: Oxford University Press; 2014.


An P, Straka RJ, Pollin TI, Feitosa MF, Wojczynski MK, Daw EW, O’Connell JR, Gibson Q, Ryan KA, Hopkins PN, Tsai MY, Lai CQ, Province MA, Ordovas JM, Shuldiner AR, Arnett DK, Borecki IB. Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response. Hum Genet. 2014 Jul;133(7):919-30. doi: 10.1007/s00439-014-1435-3. Epub 2014 Mar 7. PMID: 24604477 PMCID: PMC4112746

Frazier-Wood AC, Wojczynski MK, Borecki IB, Hopkins PN, Lai CQ, Ordovas JM, Straka RJ, Tsai MY, Tiwari HK, Arnett DK. Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their respons-es to fenofibrate. Biology (Basel). 2014 Aug 25;3(3):536-50. doi: 10.3390/biology3030536. PMID: 25157911 PMCID: PMC4192626

20

TEACHING

TEA

CH

ING

In 2014, ECP faculty mentored:

• 14 students on special research projects funded under CTSI/CHE,

Melendy Scholarships, or Undergraduate Research Opportunities Program

• 15 undergraduate students

• 13 professional students

• 18 graduate students in non-ECP programs

• 15 post-doctoral fellows or residents

In 2014, ECP faculty:

• offered clerkships or experiential instruction to 102 students

• served as advisors or readers on thesis projects to 113 pharmacy students

With more than

two dozen faculty

and a dedicated

administrative

and research

staff, ECP trains

professional,

graduate, and

post-graduate

students of the

highest caliber

while advancing a

widely respected

research program.

The College of Pharmacy consistently ranks among the top three pharmacy

schools in the nation. In 2014, ECP faculty provided 1,960 hours of didactic

education to 165 pharmacy students per class year, as well as students in den-

tistry, nursing, public health, geriatrics, and genetics. Instruction to pharmacy

students included experiential education in acute care, geriatric patient care,

pediatric infectious disease, and clinical toxicology. It also included teaching

and directing in the pharmacotherapy series and the pharmaceutical care

skills course sequence, and teaching other elective courses. In addition, ECP

members participated in journal clubs throughout the University in their areas

of interest and with research collaborators.

21

SERVICE

In addition to their college teaching and research, many ECP faculty discover

opportunities for service both within the University and with outside organi-

zations and companies. The immeasurable hours they spend offering expertise

and guidance are a way to give back to the community, peers and students, and

the field. Faculty members had appointments on boards of directors or profes-

sional advisory boards of research organizations; others had appointments on

standards and education committees with health providers in Minnesota.

In 2014, faculty reported service as manuscript reviewers for 65 journals; as

proposal reviewers for 9 funding bodies; and as reviewers of faculty promotion

documents for institutions across the country and around the world.

The hours of

service by ECP

faculty and staff

enhance the

standing of the

College in the

profession and in

the community,

and are an

opportunity

to develop

collaborations

nationally and

internationally.

SER

VIC

E

In 2014, ECP faculty:

• cited service to 31 national committees/professional organizations

• served on 34 University and AHC committees including the Faculty

Senate, the Graduate Education Council, search committees, and scientific

advisory groups

• had a total of 67 service commitments to committees within the College of

Pharmacy and 27 within ECP

22

GRADUATE PROGRAM

The ECP Graduate Program is an innovative, interdisciplinary program

that trains students to conduct research encompassing methodology from

basic and clinical pharmacology perspectives. It was designed specifically

for students interested in clinical research with the goal to advance the

science of human pharmacology and therapeutics to improve the safe,

effective, and economical use of drugs by patients. Students study such topics

as experimental pharmacotherapy, drug metabolism, infectious disease,

pharmacometrics, and pharmacogenomics. Graduates are prepared for

distinguished careers in clinical research.

ECP celebrated the graduation of four students in 2014 (bringing the total

number of program graduates to 41), and had a total of 16 new and continuing

students in the program as of Fall 2014.

GR

AD

UAT

E P

RO

GR

AM

The Graduate

Program provides

individualized

hands-on learning

experiences

to those who

will become

tomorrow’s leaders

in experimental

and clinical

pharmacology

research and

teaching.

23

Graduate Thesis Title Advisor Current Employer

Suresh Agarwal, Ph.D. Clinical Pharmacology and Pharmacometric Analyses of CNS Drugs Used in the Acute Management of Seizures and Spasticity

Jim Cloyd, Pharm.D. AbbVie, Inc.

Caroline Churchill, Ph.D. The Impact of Gene Transfer of Arginine Decarboxylase to the Central Nervous System on Opioid Analgesic Tolerance

Carolyn Fairbanks, Ph.D. University of Minnesota

Mary Holmay, Ph.D. N-acetylcysteine: Pharmacokinetics and Effects in Selected Neuro Degenerative Disorders

Jim Cloyd, Pharm.D. Upsher-Smith

Jie Zhou, Ph.D. Mitigating Oxidative Stress in Childhood Cerebral Adrenoleukodystrophy: An Investigation of N-acetylcysteine Pharmacology

Jim Cloyd, Pharm.D. Nuventra Pharma Sciences

ECP Ph.D. Graduates in 2014

New Ph.D. Candidates in 2014

Mariam Ahmed, B.D.

Taraswi Mitra Ghosh, M.Sc.

Krista Johnson, B.S.

Malek Okour, B.S.

New Students in Fall 2014

Samuel P. Callisto Advisor: Susan E. Marino, Ph.D.

Natalie S. Schmitz Advisor: Jim Cloyd, Pharm.D.

24

Presentations by Graduate Students or Post-Docs in 2014

Agarwal S. Placebo responses in research and medicine. Presented at: Center for Orphan Drug Research Seminar, College of Pharmacy, University of Minnesota; 2014 Mar 6; Minneapolis, MN.

Ahmed M. PK/PD modeling of inorganic nitrate and nitrite. Presented at: Department of Experimental and Clinical Phar-macology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Feb 12; Minneapolis, MN.

Ahmed M. Lorenzo’s oil in adrenoleukodystrophy: population PK/PD analysis. Presented at: Center for Orphan Drug Re-search Seminar, College of Pharmacy, University of Minnesota; 2014 Apr 17; Minneapolis, MN.

Alhadab A. Sertraline PK in HIV patients. Presented at: Department of Experimental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Apr 9; Minneapolis, MN.

Published Articles by Graduate Students or Post-Docs in 2014

Agarwal SK, Kriel RL, Cloyd JC, Coles LD, Scherkenbach LA, Tobin MH, Krach LE. A pilot study assessing pharmacoki-netics and tolerability of oral and intravenous baclofen in healthy adult volunteers. J Child Neurol. 2015 Jan;30(1):37-41. Epub 2014 Jul 14. PMID: 25028414

Cheng S, LeBlanc KJ, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alz-heimer’s disease. PLoS One. 2014 Oct 2;9(9):e108845. doi: 10.1371/journal.pone.0108845. eCollection 2014. PMID: 25275487 PMCID: PMC4183525

Spaulding AR, Salgado-Pabón W, Merriman JA, Stach CS, Ji Y, Gillman AN, Peterson ML, Schlievert PM. Vaccination against Staphylococcus aureus pneumonia. J Infect Dis. 2014 Jun 15;209(12):1955-62. doi: 10.1093/infdis/jit823. Epub 2013 Dec 19. PMID: 24357631 PMCID: PMC4038136

Parent MA, Hottman DA, Cheng S, Zhang W, McMahon LL, Yuan LL, Li L. Simvastatin treatment enhances NMDAR-mediated synaptic transmission by upregulating the surface distribution of the GluN2B subunit. Cell Mol Neurobiol. 2014 Jul;34(5):693-705. doi: 10.1007/s10571-014-0051-z. Epub 2014 Apr 1. PMID: 24687455 PMCID: PMC4142643

Hottman DA, Li L. Protein prenylation and synaptic plasticity: implications for Alzheimer’s disease. Mol Neurobiol. 2014 Aug;50(1):177-85. doi: 10.1007/s12035-013-8627-z. Epub 2014 Jan 5. PMID: 24390573 PMCID: PMC4082763

Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and cognition in neurodegenerative disorders. Neurobiol Dis. 2014 Dec;72 Pt A:22-36. doi: 10.1016/j.nbd.2014.07.015. Epub 2014 Aug 13. PMID: 25131449 PMCID: PMC4252583

Clark AM, Halvorsen MB, Braun TL, Johnson KM, Cloyd JC. USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. Epilepsia. 2014 Jul;55(7):1069-76. Epub 2014 May 23. PMID: 24861853 PMCID: PMC4283972

Tam HK, Kelly AS, Metzig AM, Steinberger J, Johnson LA. Xanthine oxidase and cardiovascular risk in obese children. Child Obes. 2014 Apr;10(2):175-80. doi: 10.1089/chi.2013.0098. Epub 2014 Feb 25. PMID: 24568669 PMCID: PMC3992000

25

Hottman D. Therapeutic potential of a novel neuroprotective compound TH-237A for Alzheimer’s disease. Presented at: Department of Experimental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Sep 17; Minneapolis, MN.

Johnson K. Comparison of assay methods for measurement of topiramate concentrations in blood and plasma. Presented at: Center for Orphan Drug Research Seminar, College of Pharmacy, University of Minnesota; 2014 Mar 13; Minneapolis, MN.

Johnson K. Comparison of blood and plasma assay methods for measurement of topiramate concentrations in children. Presented at: Minnesota Epilepsy Group; 2014 Sep; Minneapolis, MN.

Johnson K. Enhancing reproducibility and transparency of research findings. Presented at: Center for Orphan Drug Re-search Seminar, College of Pharmacy, University of Minnesota; 2014 Oct 23; Minneapolis, MN.

Johnson K. Use of dried blood spots to characterize topiramate disposition in children. Presented at: Minnesota Epilepsy Foundation Research Summit; 2014 Nov; Minneapolis, MN.

Lim CN. Pharmacokinetic-pharmacodynamic modeling of gonadotropin-releasing hormone analogues. Presented at: De-partment of Experimental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Oct 22; Minneapolis, MN.

Okour M. Population pharmacokinetic-pharmacodynamic analysis of mycophenolate. Presented at: Department of Exper-imental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Oct 29; Minneap-olis, MN.

Peterson C. Chronic pain and drug addiction: a behavioral overview. Presented at: Department of Experimental and Clini-cal Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Feb 19; Minneapolis, MN.

Roman Y. Health disparities in knowledge of genomics: a case example of a potential missed opportunity to improve care for hyperuricemia, gout, and CVD. Presented at: Center for Health Equity Works in Progress, University of Minnesota; 2014 Feb 25; Minneapolis, MN.

Roman Y. Contemporary management of hyperuricemia and gout and opportunities to consider pharmacogenetics. Pre-sented at: Department of Experimental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Nov 19; Minneapolis, MN.

Sanghavi K. Population pharmacokinetics of F-ARA-A in non-myeloablative stem cell transplant patients. Presented at: Department of Experimental and Clinical Pharmacology Weekly Seminar, College of Pharmacy, University of Minnesota; 2014 Mar 12; Minneapolis, MN.

Schmitz N. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. Presented at: Sarasota Memorial Hospital Student Pharmacists and Pharmacist Preceptors (Journal Club Presentation); 2014 Feb 27; Sarasota, FL.

Presentations by Graduate Students or Post-Docs in 2014, continued

26

Abstracts by Graduate Students or Post-Docs in 2014

Hottman DA, Wang Z, Li L. Therapeutic potential of a novel neuroprotective compound TH237A for Alzheimer’s disease. Presented at: Society for Neuroscience Annual Meeting; 2014 Nov 15-19; Washington, DC.

Cheng S, LeBlanc K, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzhei-mer’s disease. Poster presented at: Society for Neuroscience Annual Meeting; 2014 Nov 15-19; Washington, DC.

Chernick D, Cao D, Parent M, Zhang W, Hottman D, Cheng S, Omtri R, Kandimalla K, Li L. ApoJ/clusterin mimetic peptide as a potential therapeutic for Alzheimer’s disease. Poster presented at: Society for Neuroscience Annual Meeting; 2014 Nov 15-19; Washington, DC.

Johnson KM, Coles LD, Leppik I, Patterson EE, Vuu I, Misha U, Cloyd JC. Comparison of whole blood and plasma phar-macokinetics of intravenous topiramate in dogs with naturally-occurring epilepsy. Poster presented at: American Epilepsy Society Annual Meeting; 2014 Dec 5-9; Seattle, WA.

Schmitz N. Intravenous immunoglobulin. Presented at: Sarasota Memorial Hospital Student Pharmacists and Pharmacist Preceptors; 2014 Mar 4; Sarasota, FL.

Schmitz N. Case presentation: cannabis hyperemesis syndrome. Presented at: Mayo Clinic Health System; 2014 Apr 10; Red Wing, MN.

Schmitz N. An update to the FDA’s informed consent guidance. Presented at: Center for Orphan Drug Research Seminar, College of Pharmacy, University of Minnesota; 2014 Sep 18; Minneapolis, MN.

Zhou J. Mitigating oxidative stress in childhood cerebral adrenoleukodystrophy: an investigation of n-acetylcysteine phar-macology. Presented at: Center for Orphan Drug Research Seminar, College of Pharmacy, University of Minnesota; 2014 Jan 23; Minneapolis, MN.

Presentations by Graduate Students or Post-Docs in 2014, continued

27

Lim CN, Marino SE, Brundage RC, Birnbaum AK. Pharmacokinetics-pharmacodynamics modeling of the effect of topira-mate on working memory in healthy volunteers. Poster presented at: American Conference of Pharmacometrics; 2014 Oct 12-15; Las Vegas, NV.

Lim CN, Marino SE, Brundage RC, Leppik IE, Cloyd JC, Birnbaum AK. Pharmacokinetics-pharmacodynamics modeling of the effect of topiramate on working memory in healthy volunteers. Presented at: Rho Chi Symposium, University of Min-nesota; 2014 Mar 26; Minneapolis, MN.

Straka RJ, Roman Y, Xiong J, Lor M, Culhane-Pera K. Variability in prevalence of key single nucleotide polymorphisms (SNPs) within Asian populations underscores the importance of individualized genomic information when guiding drug therapy. Presented at: 7th Santorini Conference - Biology Prospective 2014; 2014 Sep 25-27; Santorini, Greece.

Xiong JD, Roman YM, Menk JS, Culhane-Pera K, Straka RJ. Differential prevalence of loss/gain of function alleles affect-ing response to clopidogrel in the Hmong underscores the importance of genotyping unique subpopulations as a means to address existing health disparities. Presented at: American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology 2014 Scientific Sessions; 2014 May 1-3; Toronto, Ontario, Canada. Arterioscler Thromb Vasc Biol. 2014;34:A194

Roman YM, Xiong JD, Menk JS, Culhane-Pera K, Straka RJ. Higher prevalence of risk alleles for hyperuricemia parallels el-evated incidence of gout and growing risk for cardiovascular diseases in a Hmong population. Presented at: American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology 2014 Scientific Sessions; 2014 May 1-3; Toronto, Ontario, Canada. Arterioscler Thromb Vasc Biol. 2014;34:A537

Sanghavi K, Jacobson P, Long-Boyle J, Brundage R, Kirstein M. Population pharmacokinetics of fludarabine (F-ara-A) in nonmyeloablative hematopoietic stem cell transplant (HCT) patients. Presented at: American Society for Clinical Pharma-cology and Therapeutics (ASCPT) 2014 Annual Meeting; 2014 Mar 18-22; Atlanta, GA.

Sanghavi K, Brundage R, Miller M, Schaldt D, Israni A, Guan W, Oetting W, Mannon R, Remmel R, Matas A, Jacobson P. Developing a tacrolimus dosing equation for African American kidney transplant recipients using genetic variants and clinical factors. Presented at: CTSI Poster Session & Reception, University of Minnesota; 2014 Sep 15; Minneapolis, MN. [Winner, Best Poster – Advanced Research Program]

Sanghavi K, Wiseman AC, Kirstein M, Brundage R, Jacobson PA. Phosphoramide mustard (PM) population pharmacoki-netics to estimate inter-individual variability in exposure and identify clinical factors associated with variability after reduced intensity conditioning (RIC). Presented at: 56th American Society of Hematology (ASH) Annual Meeting and Exposition; 2014 Dec 6-9; San Francisco, CA.

Wiseman AC, Sanghavi K, Cao Q, Warlick ED, Brunstein CG, Rogosheske J, Kurtzweil A, Weisdorf DJ, Jacobson PA. Association of phosphoramide (PM) and fludarabine (FLU) pharmacokinetics with treatment related mortality (TRM) after reduced intensity conditioning (RIC) hematopoietic cell transplantation (HCT). Presented at: 56th American Society of Hematology (ASH) Annual Meeting and Exposition; 2014 Dec 6-9; San Francisco, CA.

Sanghavi K, Wiseman AC, Cao Q, Warlick ED, Brunstein CG, Brundage R, Rogosheske J, Kurtzweil A, Wagner JE, Weis-dorf DJ, Jacobson PA. Pharmacokinetic modeling of fludarabine to control exposure and improve outcomes after reduced intensity conditioning transplantation. Presented at: 56th American Society of Hematology (ASH) Annual Meeting and Exposition; 2014 Dec 6-9; San Francisco, CA.

Abstracts by Graduate Students or Post-Docs in 2014, continued

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DEPARTMENT OF EXPERIMENTAL AND CLINICAL …DEPARTMENT OF EXPERIMENTAL AND CLINICAL PHARMACOLOGY Contents 2 Letter from the Department Head 4 Department Members 6 Research 20 Teaching