SCHOOL OF MEDICINE

Department of Medicine

Clinical Pharmacology

Pediatric Clinical Pharmacology Fellowship: Program Faculty

Pediatric Clinical Pharmacology Fellowship

Drs. Renbarger and Flockhart will be supported in their efforts by a broad and distinguished group of faculty. The biosketches of the entire faculty who will carry out the training described are listed below. These clinician scientists represent a balance of experienced faculty with excellent peer-reviewed funding and many years of experience with a small number of young investigators who represent the future of our Division and who are in the process of generating unique research programs supported by stable funding.

Robert Bies, Pharm.D., Ph.D. Dr. Bies is an Associate Professor in the Division of Clinical Pharmacology and the first Director of the Disease Modeling Program for the Clinical and Translational Sciences Institute at Indiana University. Before that, he served as an Assistant Professor of Pharmaceutical Sciences and Psychiatry in the Schools of Pharmacy and Medicine at the University of Pittsburgh. His research interests encompass disease modeling, pharmacometrics and quantitative pharmacology. This research comprises two primary tracks, applied and methodological. The applied stream has included disease and drug models in oncology, psychiatry, neuropathic pain, traumatic brain injury and stroke. The methodological side has focused on issues of nonlinear dynamics in physiological/pharmacological systems as well as model search and optimization. Dr. Bies has more than 30 publications in the area of modeling and simulation, in which he specialized in the study of psychiatric disorders and the disposition of psychotropics as well as methodologic issues surrounding Bayesian hierarchical approaches. He has served on special study sections for NCI and NIA and is a member of the American Association of Pharmaceutical Scientists, American College of Clinical Pharmacology and American Society for Clinical Pharmacology and Therapeutics. Dr. Bies serves as executive editor for the British Journal of Clinical Pharmacology and is on the editorial boards of the Journal of Clinical Pharmacology and the Journal of Pharmacokinetics and Pharmacodynamics. He is a Scientific Advisor for the Metrum Institute as well as the Leiden Amsterdam Center for Drug Research quadrennial In-Vivo Measurement and Modeling of Drug Effects meeting. Dr. Bies research represents an outstanding opportunity for fellows participating in this training program to obtain experience and to develop a pediatric clinical pharmacology career with a focus on modeling.


John T. Callaghan, M.D., Ph.D. Dr. Callaghan is the former Director of Clinical Pharmacology at the Eli Lilly clinical research center located in University Hospital on the IU Medical School campus. He retired after nearly 27 years at Eli Lilly in October 2005. Dr. Callaghan had maintained an active association with the Indiana University School of Medicine as a Member of the Graduate School Faculty, and is an Associate Professor in Medicine in the Division of Clinical Pharmacology, and the Department of Pharmacology and Toxicology. At Eli Lilly as a clinical pharmacologist before he was director, he had responsibility for leading drug development Phase 1 strategies from first-in-man up to new drug applications (NDAs). He led the teams and was a clinical investigator on several successful NDAs, including nizatidine (H2-antagonist), pinacidil (K+ channel opener), and olanzapine (an atypical antipsychotic). He has experience developing drugs in the fields of cardiology, gastroenterology, psychiatry, pulmonary, rheumatology, infectious disease, diabetes, and opiate pharmacology. In 1999 he was appointed Director of the Lilly Clinic and U.S. Clinical Pharmacology and had responsibility for Phase 1 programs in cardiology, endocrinology, inflammation, and aspects of oncology. Dr. Callaghan was instrumental in introducing pharmacogenetics to Lilly's drug development process, initially by CYP2D6 and NAT2 phenotyping and later by introducing pharmacogenetic testing for NAT2, CYP2D6, CYP2C9, and CYP2C19 alleles. As part of a core leadership team, he also promoted a formal biomarker program that revamped Lilly's Phase 1 development strategy. In his current academic role, he has a major responsibility for Clinical and Research Fellowship training as co-Director of the Medicine/Clinical Pharmacology T32 at our institution. He has instituted courses in Drug Development Strategy and Personalized Medicine. He also has developed a series of ongoing Clinical Case Conferences involving several subspecialty divisions and departments (Pediatrics, Oncology, Psychiatry, Obstetrics, Cardiology, Hepatology, and Infectious Disease) with the goal of generating research proposals and publications for Fellows in training.

D. Wade Clapp, M.D. Dr. Clapp is the Richard L. Schreiner Professor of Pediatrics and Chairman of the Department of Pediatrics at the Indiana University School of Medicine. He has had continuous NIH research support as a principal investigator since 1991 and is currently the PI on six R/PO1/P50 and UO1 awards. His research laboratory is focused on genetic disorders that present with a predisposition to cancer in infants and children. Dr. Clapp is internationally recognized for his research in neurofibromatosis type 1, a crippling tumor-creating disorder. He led a team that developed the first promising, non-surgical treatment for this disease, which is one of the most common genetic conditions in humans. This work has led to clinical trials that are currently ongoing and additional trials in the planning stages. Dr. Clapp has served as director of the Indiana University Medical Scientist Training Program since 2001 and has trained 17 post-doctoral fellows (see Table 5). The oldest of these individuals are now Section Chiefs and members of the American Society for Clinical Investigation. His trainees have won a number of national awards for being the outstanding trainee at their respective level including the Young Investigator Award at the National Neurofibromatosis Foundation, the American Society of Hematology (x2), the Society for Pediatric Research (x2) and the International Society of Experimental Hematology.

Scott Denne, M.D. Dr. Denne is a neonatologist with a long-standing research focus in the area of neonatal nutrition and metabolism, in particular examining the regulation of protein accretion and assessing energy requirements using stable isotope tracer techniques. In addition to his specific research focus, he has had wide ranging experience in neonatal clinical research, and is currently the Associate Director for the Indiana CTSI, where he is the Director of the Indiana Clinical Research Center, the coordinator of all pediatric activities within the CTSI, and the Chair of the Pediatric Project Development Team. He is also committed to mentoring young pediatric scientists, and over the last 10 years has mentored 8 individuals in pediatric subspecialty fellowships (Neonatology, Endocrinology, Hematology/Oncology, and Gastroenterology); 7 of these individuals currently hold faculty positions in academic institutions. He will continue to be an active mentor for this important training program.

Zeruesenay Desta, Ph.D. Dr. Desta completed his training in clinical pharmacology at Georgetown University Medical Center in the T-32 funded program led by Dr. Flockhart, and moved with the pharmacogenetics group from Georgetown to Indianapolis in the summer of 2001. He has now risen to the rank of Associate Professor in the Department of Medicine and leads an active laboratory group focused on the pharmacogenetics of Cytochrome P450 2B6. Dr. Desta has a deep background in Pharmacology, having taught the subject to the medical class at the University of Gondar in Ethiopia for several years after he obtained his Ph.D. in drug metabolism in Germany. He has been actively involved in training clinical pharmacology fellows as a part of this training program. He has organized the didactic pharmacogenetic teaching in the Division and has participated in teaching this and other courses. In addition, he is an exceptionally productive researcher who has published over 60 papers in peer-reviewed journals since the start of his fellowship and beyond. Dr. Desta's main research focus is the identification of genetic and non-genetic mechanisms of interindividual variability in drug metabolism and response, with goal of improving personalized medicine to the individual patient. He now has years of experience and expertise in conducting in vitro and in vivo drug metabolism, drug interaction and pharmacogenetics studies, particularly those drugs mediated by the cytochrome P450 system including drugs used in the therapy of HIV and breast cancer. He has initiated pharmacogenetic studies of CYP2B6 using novel tools developed in his laboratory that formed the basis for his research in the area of CYP2B6 genetic polymorphisms and drug interactions. In addition, he is a co-investigator of the Consortium on Breast Cancer Pharmacogenomics center at Indiana University, one of the components of the national Pharmacogenetics Research Network, and of an R-01 on Pharmacogenetics of Hormonal Therapy for Breast Cancer. Clinical pharmacology fellows have benefited significantly from his research expertise during the design and conduct of their research projects but also during data analysis and writing of manuscripts, as the record of publications with fellows demonstrates. Dr. Desta has served as a member of the GCRC Advisory Committee at Indiana University; of the ACTG Pharmacology section; is a consultant to the FDA Gastrointestinal Advisory Committee; and a member of Scientific Program Committee of ASCPT. Dr Desta is a committed and enthusiastic teacher in the laboratory and clinic, who will serve as a mentor for fellows in the period of this application.

Steven Downs, M.D., MS. Dr. Downs is Director of the Children's Health Services Research group at IUSM and Director of General Pediatrics. His research integrates decision sciences, health services research, and medical informatics. He is the developer of CHICA, a computer-based, decision support system that utilizes decision theoretic models and health behavior theory to improve care of children. He is the program director for two federally funded training programs in biomedical informatics and in health services research. His research includes evaluation and decision support for pediatric and chronic disease management. He has received ongoing NIH funding since 1994.

Laura Haneline, M.D. Dr. Haneline is a neonatologist and a stem cell biologist whose research focuses on how dysfunction of stem and progenitor cells impacts the pathogenesis of hematopoietic and vascular diseases. Her laboratory is actively investigating whether pathologic oxidative stress encountered by a fetus exposed to a diabetic intrauterine environment leads to altered endothelial progenitor cell function. Additionally, her laboratory demonstrated that endothelial progenitor cell subsets are reduced in cord blood and maternal blood samples from pregnancies complicated by gestational diabetes, supporting the concept that measuring endothelial progenitor cell subsets during pregnancy could serve as a biomarker to identify those at highest risk for vascular dysfunction. Based on these studies, she is involved in an NIH-funded Obstetric-Fetal Pharmacologic Research Unit Network that proposes basic and translational pharmacologic studies of drug disposition and effect on endothelial progenitor cell subsets during normal and abnormal pregnancies.

Dr. Haneline has been active in physician-scientist training her entire career. She participated in the development of the Morris Green Scholar's program at Riley Children's Hospital with the overall goal of enhancing the number of well-trained, physician-scientists from our program. She continues to serve in an advisory capacity and as a research mentor for this program. Her laboratory has supported the training of clinical fellows, post-doctoral fellows, a graduate student, and undergraduate students. Trainees in her lab publish in high-impact journals representing the quality of their work. In addition, she has served on several junior faculty mentoring committees to assist with their career development and academic promotion.

David Ingram, M.D. Dr. Ingram is a Professor of Pediatrics in the Developmental Biology Research Group. His laboratory focuses on understanding how signaling pathways control the development of hematopoietic stem and progenitor cells and how aberrations in these pathways cause human blood disorders and leukemias. Dr. Ingram's laboratory has extensive experience in utilizing genetically engineered mouse models to study childhood cancers and vascular malformations. He is the author of 99 peer reviewed publications. Dr. Ingram is the Section Director for Neonatology at IUSM, is a member of the American Society for Clinical Investigation and will be President of the Society for Pediatric Research (SPR) in 2011. He is an NIH funded physician-scientist with two R01s and a U01 and is co-investigator on two P01/P50s. Dr. Ingram is one of the basic/ translational scientists with whom fellows supported by this program will have the opportunity to do research. He also serves on the advisory committee for this fellowship training program.

Lang Li, Ph.D. Dr. Li's research profile has been built upon computational pharmacology, a unique expertise in the inter-disciplinary area between pharmacology and biostatistics/bioinformatics, since his Ph.D. training at the University of Michigan. His solid background in mathematics and statistics enables him to develop statistical theory and computational algorithms for the physiologically-based pharmacokinetic (PBPK) models. His research in this area is currently funded by NIGMS. Since joining Indiana University in 2001, his research has been expanded to molecular pharmacology and genetics research areas, including drug interactions, pharmacogenetics, and epigenetics in drug metabolism. Dr. Li has established multiple collaborations with basic and clinical researchers (including multiple pediatric faculty members) which have been instrumental in providing the necessary information required for identification of the key factors for drug exposure predictions. In the mean time, he has also applied PK models to investigate drug exposures in different patient population including: breast cancer, pediatric leukemia, autism, AIDS, hypertension, and pregnancy. He has also developed extensive bioinformatics skills in genomics, epigenetics, and text mining. Dr. Li teaches statistical genetics and population pharmacokinetics courses and has been actively involved in clinical pharmacology fellow's training since he joined IU in 2001. He provides the introductory statistical lectures to fellows and is a regular source of statistical consultation for every fellow in the Division of Clinical Pharmacology. Dr. Li has mentored one Ph.D. student who graduated from Biostatistics currently is chairing three Ph.D. candidates who are majoring in biostatistics, bioinformatics, and molecular pharmacology, respectively, and their thesis topics are pharmacokinetics/pharmacogenetics related modeling and data mining problems. Dr. Li is also either the mentor or co-mentor of two additional postdoctoral students. Given his extensive computational, pharmacology and genetics background, Dr. Li represents a critical component of this training grant application.

David R Jones, Ph.D. Dr. Jones is an Assistant Scientist in the Division of Clinical Pharmacology in the Department of Medicine at Indiana University. Prior to coming to Indiana University he worked at CIBA-Geigy after he completed a fellowship in Clinical Pharmacology at Vanderbilt University. Dr. Jones's research involves studies in drug metabolism, the inhibition of drug metabolism (mechanism-based and reversible), and predictions of in vivo effects from in vitro studies. He is currently a co-investigator on five grants and a PI of a shared facility that is part of the NCI Cancer Center grant. His research has resulted in over 40 publications. Dr. Jones oversees the laboratory work of many students and fellows that work in the Division of Clinical Pharmacology and has directed the laboratory supervision of 14 students and eight fellows since he arrived at Indiana University. In addition, he has served on one dissertation committee, four qualifying exam committees, and three master's thesis committees.

Dr. Jones is also the Director of an analytical laboratory, the Clinical Pharmacology Analytical Core laboratory, that is an Indiana University School of Medicine core laboratory as well as an Indiana University Cancer Center core laboratory. This laboratory has provided opportunities for fellows to be exposed to pharmacokinetic data of studies in early cancer clinical trials. Dr. Jones is the coordinator for the drug metabolism/pharmacokinetic section in the Introduction to Pharmacology and Toxicology course which is group taught by the Department of Pharmacology and Toxicology. Dr. Jones also teaches mechanisms of drug inhibition (metabolism and transport) as part of another class sponsored by the Department of Pharmacology and Toxicology. Dr. Jones presents four lectures on bioanalytical approaches to clinical studies to fellows in the Division of Clinical Pharmacology. Currently, he serves as the Vice Chairman of one Institutional Review Board at IUPUI and has served on the executive committee of the IRB at IUPUI and therefore serves as a valuable source of experience and expertise on regulatory matters for trainees. Dr. Jones is also the Indiana University representative to the United States Pharmacopeia.

Eric M. Meslin, Ph.D. Eric Meslin is Director of the Indiana University Center for Bioethics; Professor of Medicine, and of Medical and Molecular Genetics in the Indiana University School of Medicine; and Professor of Philosophy in the School of Liberal Arts. He is also Assistant Dean for Bioethics at the Indiana University School of Medicine. He came to Indiana University in July 2001 from the National Bioethics Advisory Commission (NBAC), where he had been Executive Director since 1998. NBAC was appointed by President Bill Clinton in 1995, and was charged with advising the White House and the federal government on a range of bioethics issues including cloning, stem cell research, international clinical trials, and genetics studies. Dr. Meslin has held academic positions at the University of Toronto and at the University of Oxford. From 1996-98 he was Program Director for Bioethics Research in the Ethical, Legal and Social Implications (ELSI) Research Program at the National Human Genome Research Institute in Bethesda, Maryland. He has authored (or co-authored) more than 80 articles and book chapters, with most focusing on various topics in research ethics and health policy. He has been a consultant to the World Health Organization, and the US Observer Mission to UNESCO and is a member of a number of advisory boards, including the Board of Directors of the Canadian Stem Cell Network, and the Stem Cell Oversight Committee of Juvenile Diabetes Research International. He is co-editor of the Bioethics and the Humanities Series published by Indiana University Press.

Todd Skaar, Ph.D. Dr Skaar is an Associate Research Professor in the Division of Clinical Pharmacology. He was recruited to Indiana University School of Medicine by Dr. Flockhart from Georgetown University, where he completed his post-doctoral training in the laboratory of Robert Clarke, Ph.D. in the Lombardi Cancer Center. While at Georgetown, he was promoted to the faculty and also became the director of the DNA sequencing core. He is a highly skilled molecular biologist with interests in molecular pharmacology and pharmacogenetics. Dr. Skaar's research program provides an extensive training resource in pharmacogenetics and pharmacogenomics. His research is currently funded by several external peer-reviewed research grants for which he is PI and Co-I. These grants are from agencies such as NIGMS, NCI, NCRR, and the Department of Defense (See Table 4). The grants are focused primarily on the pharmacogenetics of therapies used in oncology, such as endocrine therapies and antidepressants as well as micro RNA expression patterns that are associated with the documented developmental changes in the drug-metabolizing enzyme: CYP2D6. His laboratory provides additional laboratory and intellectual resources that are also available for the training of fellows. Dr. Skaar represents an important component of our proposed training program for fellows interested in pharmacogenetics and pharmacogenomics. He teaches the basic molecular biology concepts in a series of formal and informal settings during the year. Furthermore, the fellows receive much of their practical training in molecular genetics and molecular pharmacology training in Dr. Skaar's laboratory. His laboratory is equipped with state of the art equipment facilities for conducting genetics, molecular biology and cell culture experiments.

Steven Steiner, M.D., MS. Dr. Steiner is an Associate Professor of Pediatrics in the Division of Pediatric Gastroenterology/Hepatology/Nutrition. His translational research examines substrate metabolism, including whole body and tissue specific protein metabolism, in pediatric patients with inflammatory bowel disease. Utilizing stable isotope infusion and mass spectrometry techniques, pediatric patients are studied in response to nutritional and medical therapy. He has received NIH funding since 2005.