Laboratories: Clinical Pharmacology Analytical Core Second Annual Harry and Edith Gladstein Professor Thomas Hudson, MD President and Scientific Director, OICR 1:00pm May 25, 2010 R3-203 Auditorium New Seminar Series (August 2008) Personalized Therapeutics Fellowship Training Opportunities Available July 2008 The Division of Clinical Pharmacology at the Indiana University School of Medicine seeks candidates with Internal Medicine, Pediatric or Psychiatry residency training for a two to three year NIH-sponsored program of research training in Clinical Pharmacology and Pharmacogenomics which prepares trainees for careers as independent investigators in academia, industry or government. Candidates for NIH sponsorship must be US citizens or permanent residents with an M.D., PharmD or Ph.D. degree and projected completion of residency training. Trainees may be eligible for $35,000 of loan reimbursement per year during their training via the NIH Clinical Research Loan Reimbursement program. Salaries are competitive and based on the NIH scale for post-graduate training. Inquiries to: John T. Callaghan, MD, PhD, 1001 West 10th Street, WD Myers W7123, Indianapolis, IN 46202 or jcallagh@iupui.edu Dr. Renbarger Studies Vincristine Jamie Renbarger, M.D., has made two new discoveries with a drug that was approved in 1963, opening the door to new knowledge that may further help children with cancer. Renbarger knew that vincristine -- which is widely used to treat cancers in children – led to side effects that varied considerably between patients. But why? In the lab, she discovered that two enzymes, CYP3A5 and CYP3A4, metabolize vincristine differently. CYP3A5, which is found in approximately 70 percent of African-Americans and 10 percent to 20 percent of Caucasians, metabolizes vincristine much more efficiently than CYP3A4. Knowing which enzymes to target, Renbarger next compared toxicity in Caucasians with African Americans who had Acute Lymphoblastic Leukemia. She showed that Caucasians developed side effects – such as jaw pain, loss of reflexes, and constipation -- with vincristine more often than African-Americans possibly due to the fact that the CYP3A5 enzyme is found in fewer Caucasians. Currently, Renbarger is enrolling 140 children with preB acute lymphoblastic leukemia to determine the optimal dosing of vincristine for pediatric patients, which may improve survival for young cancer patients. Renbarger’s studies tie into the Best Pharmaceuticals for Children Act (BPCA), which established a process for studying drugs used in children with the goal of improving pediatric therapeutics. Vincristine has been identified as a priority drug to study. Because of the ongoing studies at the IU Simon Cancer Center, Renbarger and her team are generating data unlike any other research currently underway.

David A. Flockhart, M.D., Ph.D. Division Chief

The Division of Clinical Pharmacology, located on the 7th floor of Wishard Hospital, is located within a rich and diverse research environment and one of the largest clinical environments in the country within the Indiana University Department of Medicine. Our division has a clinical and research focus on individualized response to drug therapy. Our mission is to carry out research and clinical activities that improve rational therapy for the treatment of disease, regardless of age, gender or ethnicity. We are particularly interested in differences in response to drug treatment that exist on the basis of age or gender or ethnic origin. To this end, our research covers a broad range of specific areas of expertise including the effects of drug and herbal interactions and pharmacogenetics on therapy in the elderly, women and children. With funding from the Food and Drug Administration, National Institutes of Health and the Pharmaceutical Research and Manufacturers of America, we have a well-funded research and training program.

Our division has a long and distinguished history. Clinical Pharmacology was originally established at the Lilly Laboratory for Clinical Research in 1970. In 1986, the Division of Clinical Pharmacology was established within the Department of Medicine under the leadership of D. Craig Brater, MD. At this juncture, the program became a joint effort that broadened the options for training pathways and research collaboration. Dr. Brater led the Division for 15 years until 2001, when David A. Flockhart, M.D., Ph.D. was appointed as his successor, and brought a pharmacogenetics group with him, thus further broadening and deepening the opportunities for both research and training. The Division now represents one of the strongest training programs in Clinical Pharmacology in the United States including fellows and graduate students, strong research programs in pharmacogenetics, drug metabolism, and drug interactions and clinical research collaborations focused in the areas of cancer, psychiatry, pediatrics and women's health.