Thesis Defense- Kelly Anne Martin
Title: Identifying and evaluating mechanisms of drug resistance in bladder cancer
Abstract: Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to resistance of gemcitabine therapy in advanced urothelial carcinoma. Transcriptomic profiling of passage 4 (P4) bladder cancer xenograft tumors from two PDX lines was performed by RNA-sequencing analysis, before and after relapse following a 21-day cisplatin/gemcitabine drug treatment regimen. Further analysis identified methionine adenosyltransferase 1a (MAT1A) to be one of the top enriched genes in a statistically significant fashion following chemotherapy relapse in both unique xenograft lines. Here, we have shown and further validated that members of the methionine metabolism pathway including both methionine adenosyltransferase 1a (MAT1A) and nicotinamide N-methyltransferase (NNMT) play an important role in contributing to drug resistance. Work presented includes identification and validation of MAT1A’s role in gemcitabine mediated drug resistance through alterations in cell proliferation and the ability to persist following drug treatment.
Monday, November 4, 2019 at 1:00pm to 3:00pm
Building D, 301
4000 Reservoir Road, N.W., Washington