Ramin Nazarian

Ramin Nazarian
Department of Medicine,David Geffen School of Medicine at UCLA
My earlier research work was focused on identifying oncogenic markers and elucidating the mechanisms of acquired drug resistance in melanoma. As part of a translational cancer research team, I was involved in the clinical trials of targeted therapy for malignant melanoma using vemurafenib, a very promising novel BRAF inhibitor (Plexxikon/Roche) that was FDA-approved in 2011 for treatment of late stage melanoma. Although majority of the patients treated with vemurafenib show an unprecedented clinical response, however, drug resistance frequently develops. Utilizing genomic and epigenetic profiling, we further characterized patient tumors, and discovered 2 novel mechanisms of acquired resistance. These mechanisms consisted of a previously unknown NRAS Q61K mutation and upregulated PDGFR? receptor, which led to a seminal first-author Nature publication. My findings have directly led to the development of additional targeted therapies currently being used for treatment of melanoma patients. PDGFR? overexpression was found to confer drug resistance in about 40% of the patient tumors. My preliminary findings have implicated an epigenetic pathway underlying the PDGFR? upregulation in a significant number of melanoma patients. Identification of these epigenetic alterations will be critical in understanding melanoma pathogenesis and overcoming the drug resistance, and therefore it could aid in the development of next generation cancer therapies.
Research Interest
My main research goals are focused on cancer epigenetics and translational cancer research, specifically deciphering the underlying genomic and epigenetic mechanisms of melanoma pathogenesis and drug resistance in order to develop novel targeted therapies for skin cancer and other malignancies.