Gerald Denis, Ph.D.
Department of Medicine, Section of Hematology and Medical Oncology
Shipley Prostate Cancer Research Center
Ph.D.: University of California Berkeley
Mechanisms of Transcriptional Control Mediated Through the Activators and Chromatin Regulators Called Bromodomain Proteins
Our research investigates the Bromodomain and ExtraTerminal (BET) proteins, epigenetic factors comprising BRD2, BRD3 and BRD4, which are critical regulators of metabolism and inflammation. This family is also important for cellular invasion, migration and epithelial-to-mesenchymal transition (EMT) in triple negative breast cancer and other cancer types, including castration-resistant prostate cancer. Recent insights into networks of abnormal immune signals in the prostate and breast cancer microenvironment suggest new avenues for research. In particular, extensive data document Type 2 diabetes as a chronic inflammatory condition. Type 2 diabetes, a common co-morbidity among our cancer patients at Boston Medical Center, likely reprograms the tumor microenvironment and the patient systemically. The dysregulated cytokine, chemokine and immune exhaustion pathways seen in our cancer patients elicit more dangerous properties from tumor cells, promoting invasion, EMT and metastases. We are developing and testing new small molecule inhibitors of the BET proteins that are more selective than the first-generation molecules like JQ1, which have created confusion because they target all the family members. Our data reveal that each family member has its own functions and they often oppose each other in critical transcriptional programs. Proper inhibition of BET proteins should break a cycle of inflammation and abnormal metabolism that promotes cancer progression. Our goal is to use new, more selective agents to reduce mortality from breast and prostate cancer by preventing metastatic disease.
Phone: 617-414-1371; Fax: 617-638-5609