Gerald V. Denis, PhD
Professor
Boston University School of Medicine
Dept of Medicine
Hematology & Medical Oncology

PhD, University of California, Berkeley
MSc, University of Tokyo




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.

More detailed study of these pathways, in African American women in particular, is essential. Risks for breast cancer incidence and progression are not distributed evenly in the population, and are likely stratified by abnormal metabolism such as is found in Type 2 diabetes; yet, the current standard of care in breast oncology does not fully consider the role of diabetes and obesity-associated inflammation as drivers of progression and metastasis. African American women bear a disproportionate burden of poor-prognosis triple negative breast cancer, as well as higher prevalence of obesity, obesity-driven Type 2 diabetes and chronic inflammation, compared to white women. Deeper mechanistic and clinical studies must focus on these more vulnerable patients.

Molecular models and population studies also 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 must consider drivers of metastasis, and the role the BET bromodomain proteins play in regulating metastasis potential. We hypothesize the BET proteins are equally important for breast cancer progression in lean women with metabolic disease and its associated chronic inflammation.

Recently, we have also explored the role of the BET bromodomain proteins in advanced prostate cancer, particularly in men with similar co-morbid conditions such as obesity and Type 2 diabetes. These inflammatory conditions also promote tumor progression in androgen-independent prostate cancer, eliciting greater cell migration and invasion, and raising the risk of metastasis. Advanced prostate cancer is a complex, heterogenous disease, with varying functional states of the androgen receptor and expression patterns across individual tumor cells. As the disease progresses, prostate tumor cells can become less reliant on androgen receptor signaling and use alternative signaling mechanisms to sustain growth and dissemination. Several of the pathways of progression are also relevant to triple negative breast cancer. Work in our lab is identifying ‘druggable’ BET protein targets to block prostate cancer progression in tumors that are either reliant on, or independent of, androgen receptor signaling. The research will benefit men with advancing prostate cancer, for whom initial therapeutic regimens have lost efficacy.

Professor
Boston University School of Medicine
Pharmacology & Experimental Therapeutics


Co-Director
Boston University
BU-BMC Cancer Center


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Full Member
Boston University Medical Center
Boston Nutrition Obesity Research Center


Member
Boston University
Family Medicine


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences




Multiscale Analysis of Metabolic Inflammation as a Driver of Breast Cancer
09/09/2020 - 08/31/2025 (Multi-PI)
PI: Gerald V. Denis, PhD
NIH/National Cancer Institute
1U01CA243004-01A1

Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer
08/07/2018 - 07/31/2023 (PI)
NIH/National Cancer Institute
5R01CA222170-03

Uncoupling Obesity from Breast Cancer in African American Women
09/01/2016 - 08/31/2020 (Multi-PI)
PI: Gerald V. Denis, PhD
NIH/National Cancer Institute
5U01CA182898-05

Uncoupling Obesity from Breast Cancer in African American Women
09/24/2013 - 08/31/2016 (Multi-PI)
PI: Gerald V. Denis, PhD
NIH/National Cancer Institute
5U01CA182898-03

Mechanisms of Brd2 Immunoprotection for Insulin Resistance
09/30/2011 - 08/31/2013 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
1R56DK090455-01A1

Mechanisms of Brd2 Immunoprotection for Insulin Resistance
09/30/2011 - 08/31/2013 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
1R56DK090455-01A1

Ultrasound-Directed Delivery of Cancer Chemotherapeutic Drugs
01/01/2009 - 12/31/2009 (PI)
Massachusetts General Hospital DOD Army Med Resrch

Proteomic Biomarkers for Lymphoma
06/01/2007 - 05/31/2009 (PI)
NIH/National Cancer Institute
5 R03 CA128006 02

The Role of Brd2 in Energy Homeostasis
04/01/2007 - 03/31/2009 (PI)
Massachusetts General Hospital Boston Diab Endo Res

Molecular Analysis of BRD2 Signaling and B Cell Function
01/01/2005 - 12/31/2008 (PI)
American Cancer Society

Showing 10 of 12 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2020 Multiscale analysis of metabolic inflammation as a driver of breast cancer 1U01CA243004-01A1
2020 Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer 5R01CA222170-03 2
2019 Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer 5R01CA222170-02 2
2018 Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer 1R01CA222170-01A1 2
2017 Uncoupling obesity from breast cancer in African American women 5U01CA182898-05 47
2016 Uncoupling obesity from breast cancer in African American women 4U01CA182898-04 47
2015 Uncoupling obesity from breast cancer in African American women 5U01CA182898-03 47
2015 Uncoupling obesity from breast cancer in African American women 3U01CA182898-02S1 47
2014 Uncoupling obesity from breast cancer in African American women 5U01CA182898-02 47
2013 Uncoupling obesity from breast cancer in African American women 1U01CA182898-01 47
Showing 10 of 31 results. Show All Results

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

iCite Analysis       Copy PMIDs To Clipboard

  1. Lombardi FL, Jafari N, Bertrand KA, Oshry LJ, Cassidy MR, Ko NY, Denis GV. Novel semi-automated algorithm for high-throughput quantification of adipocyte size in breast adipose tissue, with applications for breast cancer microenvironment. Adipocyte. 2020 Dec; 9(1):313-325.View Related Profiles. PMID: 32633194
     
  2. Shafran JS, Jafari N, Casey AN, Gyorffy B, Denis GV. BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2020 Jul 21.View Related Profiles. PMID: 32690869
     
  3. Andrieu GP, Shafran JS, Smith CL, Belkina AC, Casey AN, Jafari N, Denis GV. BET protein targeting suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer and elicits anti-tumor immune response. Cancer Lett. 2019 11 28; 465:45-58.View Related Profiles. PMID: 31473251
     
  4. Dean LT, Ransome Y, Frasso-Jaramillo L, Moss SL, Zhang Y, Ashing K, Denis GV, Frick KD, Visvanathan K, Schmitz KH. Drivers of cost differences between US breast cancer survivors with or without lymphedema. J Cancer Surviv. 2019 Oct; 13(5):804-814. PMID: 31446591
     
  5. Shafran JS, Andrieu GP, Györffy B, Denis GV. BRD4 Regulates Metastatic Potential of Castration-Resistant Prostate Cancer through AHNAK. Mol Cancer Res. 2019 08; 17(8):1627-1638. PMID: 31110158
     
  6. Denis GV, Sebastiani P, Bertrand KA, Strissel KJ, Tran AH, Slama J, Medina ND, Andrieu G, Palmer JR. Inflammatory signatures distinguish metabolic health in African American women with obesity. PLoS One. 2018; 13(5):e0196755.View Related Profiles. PMID: 29738558
     
  7. Andrieu GP, Shafran JS, Deeney JT, Bharadwaj KR, Rangarajan A, Denis GV. BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment. J Leukoc Biol. 2018 08; 104(2):265-274.View Related Profiles. PMID: 29493812
     
  8. Andrieu GP, Denis GV. BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition. Mol Cancer Res. 2018 04; 16(4):580-586. PMID: 29437854
     
  9. 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.View Related Profiles. PMID: 29141994; DOI: 10.1158/0008-5472.CAN-17-1903;
     
  10. 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.View Related Profiles. PMID: 28840653
     
Showing 10 of 62 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 62 publications over 24 distinct years, with a maximum of 8 publications in 2016

YearPublications
19811
19861
19912
19961
19982
20002
20014
20021
20031
20051
20063
20081
20093
20103
20111
20124
20137
20144
20151
20168
20173
20183
20193
20202
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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