I am a molecular oncologist with experience in chromatin control of transcription in cancer. I pioneered studies of the BET bromodomains proteins, a family comprised of BRD2 (originally named RING3), BRD3 and BRD4 in somatic cells, which are important as transcriptional co-regulators. I was the first to report a function for a BET protein, and to link these co-regulators to human cancer. The BET protein field has grown from sixteen papers, when I first published my work, to over 1,300 to date; they have since been implicated in several cancer types. Our recent data have established that BET bromodomain proteins provide a functional link between abnormal metabolism, inflammation and breast cancer progression in post-menopausal African American women. We are now realizing that BET proteins regulate cytokine/chemokine production in the immune cells that infiltrate the breast cancer microenvironment, which are important for immune exhaustion, chemoresistance and metastasis.
Molecular models and population studies now suggest that metabolic disease and its associated imbalances in cytokines are more important for breast cancer initiation and progression than obesity per se. My intensive involvement over the last eight years with collaborators in population science, immunology, endocrinology and molecular oncology have prompted me to investigate a new area of high public health significance: breast cancer in non-obese women with metabolic disease and chronic inflammation. New thinking is required because the current standard of care in breast oncology does not fully consider the role of Type 2 diabetes, cardiovascular disease and their associated chronic inflammation as drivers of metastasis; furthermore even a slight increase in hazard ratio for cancer risk will affect many thousands of people — the newly at-risk population easily exceeds 1 billion, primarily in Asia.
- Associate Professor, Pharmacology & Experimental Therapeutics, Boston University School of Medicine
- Center Faculty Member, Cancer Research Center, Boston University School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- University of California, Berkeley, PhD
- University of Tokyo, MSc
- Harvard College, AB
- Published on 11/15/2017
Palmer JR, Castro-Webb N, Bertrand K, Bethea TN, Denis GV. Type II Diabetes and Incidence of Estrogen Receptor Negative Breast Cancer in African American Women. Cancer Res. 2017 Nov 15; 77(22):6462-6469. PMID: 29141994.
- Published on 8/25/2017
Denis GV, Sebastiani P, Andrieu G, Tran AH, Strissel KJ, Lombardi FL, Palmer JR. Relationships Among Obesity, Type 2 Diabetes, and Plasma Cytokines in African American Women. Obesity (Silver Spring). 2017 Nov; 25(11):1916-1920. PMID: 28840653.
- Published on 4/13/2017
Denis GV, Palmer JR. "Obesity-Associated" Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk. Cancer Prev Res (Phila). 2017 May; 10(5):267-269. PMID: 28408379.
- Published on 12/19/2016
Charlot M, Castro-Webb N, Bethea TN, Bertrand K, Boggs DA, Denis GV, Adams-Campbell LL, Rosenberg L, Palmer JR. Diabetes and breast cancer mortality in Black women. Cancer Causes Control. 2017 Jan; 28(1):61-67. PMID: 27995352.
- Published on 9/20/2016
Andrieu G, Tran AH, Strissel KJ, Denis GV. BRD4 Regulates Breast Cancer Dissemination through Jagged1/Notch1 Signaling. Cancer Res. 2016 Nov 15; 76(22):6555-6567. PMID: 27651315.
- Published on 9/13/2016
Strissel KJ, Nicholas DA, Castagne-Charlotin M, Ko N, Denis GV. Correction to "Barriers to Obtaining Sera and Tissue Specimens of African-American Women for the Advancement of Cancer Research". Clin Med Insights Womens Health. 2016; 9:35. PMID: 27695380.
- Published on 8/4/2016
Nicholas DA, Andrieu G, Strissel KJ, Nikolajczyk BS, Denis GV. BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer. Cell Mol Life Sci. 2017 Jan; 74(2):231-243. PMID: 27491296.
- Published on 7/21/2016
Andrieu G, Belkina AC, Denis GV. Clinical trials for BET inhibitors run ahead of the science. Drug Discov Today Technol. 2016 Mar; 19:45-50. PMID: 27769357.
- Published on 7/14/2016
Strissel KJ, Nicholas DA, Castagne-Charlotin M, Ko N, Denis GV. Barriers to Obtaining Sera and Tissue Specimens of African-American Women for the Advancement of Cancer Research. Clin Med Insights Womens Health. 2016; 9(Suppl 1):57-61. PMID: 27441007.
- Published on 3/23/2016
Deeney JT, Belkina AC, Shirihai OS, Corkey BE, Denis GV. BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic ß-Cell. PLoS One. 2016; 11(3):e0151329. PMID: 27008626.
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