Date Posted: Jan 18, 2022
Application Deadline: Feb 22, 2022
This is a full time (>40h/wk; hours vary) post-doctoral fellow position in a cancer research lab at Brigham and Women's Hospital with a close relationship to Dana-Farber Cancer Institute. We focus entirely on a rare aggressive and incurable cancer called NUT carcinoma, a disease we characterized both genetically and clinically. This squamous cancer is driven by a fusion oncoprotein, BRD4-NUT. We have recently discovered a small molecule bromodomain inhibitor that differs from most in that it is selective for the second bromodomain of BRD4, and while maintaing potent anti-proliferative activity in NUT carcinoma, in vitro and in vivo, it is much less toxic than first generation pan-BET inhibitors that have largely failed clinical trials. Interestingly, this inhibitor is not active in the majority of other cancers and thus the project is to determine mechanistically why NUT carcinoma is much more sensitive to selective second bromodomain inhibition than 'normal' cells or other cancer cells. Our hypothesis is that BRD4-NUT, in contrast to BRD4, is more dependent on its second bromodomain for chromatin binding. The post-doc will perform chromatin and proteomic analyses to test this hypothesis.