Steven R. Grossman, MD, PhD
Year elected: 2014
Current membership category: Senior
Virginia Commonwealth University
1201 East Marshall Street, 11-217
Richmond, VA 23298
United States of America
My longstanding interest has been to dissect the regulation of the p53 tumor suppressor network and develop novel cancer therapeutic targets that lend cancer cell specificity in tumors where the p53 network has been disrupted. My particular focus has been on factors that regulate p53 stability, such as ARF, MDM2, p300, and CBP. My laboratory was the first to identify factors that enhance the polyubiquitination and degradation of p53, extending the paradigm of known core regulators of p53 stability beyond MDM2. These “E4” factors include the p300 and CBP coactivators, which were previously known to function as acetyltrasferase coactivators of p53 in stress responses. I have also had a longstanding interest in studies examining how the ubiquitin/proteasome system regulates p53-mediated responses of normal and transformed cells to various forms of genotoxic stress and how p53 is “delivered” to the proteasome by adaptor proteins, such as hHR23A/B. More recently, our studies of the ARF tumor suppressor led us to a novel ARF-interacting factor and potential oncotherapeutic target, C-terminal binding protein (CtBP). My laboratory was the first to demonstrate the utility of the CtBP dehydrogenase as a therapeutic target in cancer, and since then, we have actively pursued the development of anti-CtBP therapeutics using both structure-based and high-throughput screening approaches.