Senior Research Professor of Medicine
Dept. of Medicine IU Simon Cancer Center Adjunct Professor, Dept. of Cellular & Integrative Physiology, IUSM
Medical Countermeasures Against Radiation
I am a radiobiologist/experimental hematologist with 22yrs experience focused on radiation effects on hematopoiesis, hematopoietic reconstitution, and hematopoietic stem cell (HSC) biology. My lab aims to better understand hematopoietic reconstitution following myeloablation for improved clinical utility in HSC transplantation, endogenous reconstitution, and other situations where patients are in need of HSC support. Towards this goal, I have gained extensive experience in all aspects of HSC biology, radiation effects on hematopoietic reconstitution, and long-term effects of radiation exposure on HSC and hematopoiesis. I have developed, extensively characterized, and validated total and partial-body irradiation mouse models of the hematopoietic acute radiation syndrome (H-ARS) in pediatric, adult, and geriatric C57BL/6 mice, as well as in adult Jackson Diversity Outbred (JDO) mice. Using these models, I have tested the survival efficacy of 56 medical countermeasures (MCM) in >150 efficacy screening studies, 21 MCM in >75 dose and/or schedule optimization studies, >12 different MCM combinations in polypharmacy studies, and performed 3 PK studies and 1 GLP-compliant survival study. My radiation work has contributed to the recent FDA licensure of Neupogen to treat lethally-irradiated personnel. I have been involved in several interactions with the FDA to discuss model development and pre-IND packages for promising MCM, and our mouse H-ARS model may undergo qualification as Drug Development Tools (DDT) by the FDA and Center for Drug Evaluation and Research (CDER). In addition to H-ARS models, I have developed a murine model for the delayed effect of acute radiation exposure (DEARE) in survivors of H-ARS and have used this model to characterize hematopoietic DEARE (known as residual bone marrow damage) and multi-organ DEARE, and to assess effects of MCM.