Research Abstract

Dr. Sara Buhrlage is an Assistant Professor in Dana-Farber’s Cancer Biology Department and HMS’s Biological Chemistry and Molecular Pharmacology Department. Sara completed a Ph.D. in organic chemistry in 2008, under the direction of Prof. Anna Mapp, from the University of Michigan where she successfully designed, synthesized and characterized small molecules that bind the transcriptional co-activator CBP and upregulate transcription when tethered to DNA. Following completion of her Ph.D. Sara trained for two years in medicinal chemistry at the Broad Institute. There she led a team of 6 chemists performing lead optimization on a macrocycle inhibitor of the hedgehog protein which resulted in analogs with superior potency, improved metabolic stability, excellent in vivo pharmacokinetics and no in vitro safety liabilities. In 2010 she joined the medicinal chemistry core at Dana-Farber Cancer Institute as a staff scientist where she quickly advanced from an entry level position to Lead Scientist, the highest non-academic track position within the Institute, before accepting a faculty appointment. In the core group Sara collaborated with cancer biologists and clinicians to pharmacologically validate novel targets of disease in vitro and in vivo and study mechanisms of disease and drug resistance. During her time in this group, Sara co-authored 12 publications and wrote 10 funded grant applications allowing the medicinal chemistry core to be financially independent less than four years after opening. In sum, Sara has established herself as leader in inhibiting ‘undruggable’ cancer targets using both direct and indirect methods. In her independent position she is using this expertise to study the regulation of proteostasis via the ubiquitin proteasome system, with a focus on deubiquitylating enzymes (DUBs) and cancer oncoproteins.