Genetic differences and developmental changes dramatically impact drug metabolism. During my clinical fellowship in pediatric gastroenterology at The Children's Hospital of Philadelphia, the frequently overlooked impact of variation in drug metabolism on the success of therapeutic regimes fascinated me. This led me to pursue laboratory research as an NRSA post-doctoral fellow during the final two years of my fellowship. These experiences focused on pharmacology but did not explore the underlying molecular mechanism of inter-patient differences in response to therapeutics. Thus, I subsequently, pursued a position that would allow me to develop the skills to study pharmacogenetics. My current position provides me the opportunity to work and be mentored in a lab with a proven history of pharmacogenetics research under Drs. Mines and McCarver. My goal is to develop a research program exploring the pharmacogenetics and ontogeny of ABC tranporters. Using a guided apprenticeship model, augmented with a targeted didactic program, I will complete a research project that will explore the role of genetic variation of ATP Binding Cassette (ABC) Transporters on thiopurine therapy - an understudied area. Thiopurines are important therapeutics used in adults and children for many diseases with significant variation in pharmacokinetics and a high rate of toxicity and treatment failure. This project will identify the common genetic variants of key thiopurine transporters and explore their impact on therapeutic response in Inflammatory Bowel Disease patients. The data generated by this project will help improve individualized treatment strategies for thiopurines, in concert with the goals of the Pharmacogenetics Research Network of NIGMS. This experience will also allow me to develop the skills to become an independent investigator focused on the pharmacogenomics of drug transporters. The proposed project is directly relevant to public health. By understanding how genetic variation impacts drug transporter function, treatment strategies for important and commonly used drugs whose bioavailability is significantly determined by transporters can be improved and individualized. This project will provide the basic scientific knowledge that can allow the clinician select the most appropriate drug and dose for an individual patient based on genetic factors. ? ? ? ? ? ?
| Biank, Vincent F; Sheth, Mehul K; Talano, Julie et al. (2011) Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis. J Pediatr 159:808-12 |
