The University of Texas MD Anderson Cancer Center
Department of Experimental Therapeutics
My research focuses on pre-clinical and clinical development of novel strategies for leukemia therapy. Specifically I have been investigating inhibitors of transcription, RNA splicing and translation in cancer therapy and overcoming drug resistance, as well as mechanism based drug combinations. These inhibitors include cyclin dependent kinase 9 inhibitors that inhibit transcription, such as flavopiridol, SNS-032 and TG02; protein synthesis inhibitors, such as homoharringtonine and Pateamine A analogs. We hypothesized that by inhibiting transcription and translation, oncoproteins with rapid turnover rate would decrease rapidly. In selected biological context where the leukemic cells are dependent on the continuous expression of such proteins for survival, these agents would effectively induced apoptosis. Mechanism-based combination of these inhibitors with either specific kinase inhibitor or apoptosis control proteins demonstrated strong synergy. Our studies led to clinical evaluation of these agents in leukemia, and we continue to evaluate the action of these compounds in the pharmacodynamics studies in the clinical trials. Aberrant RNA splicing regulation is a novel area of cancer research; we are currently studying how splicing inhibitors affected the survival proteins to induce apoptosis in the leukemia cells.
Education & Training
PhD, MD Anderson UTHealth Graduate School, 2002