Gerald V. Denis, PhD
Shipley Prostate Cancer Research Professor
Boston University Chobanian & Avedisian School of Medicine
Medicine
Hematology & Medical Oncology

PhD, University of California, Berkeley
MSc, University of Tokyo
AB, Harvard College



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.

Diversity, Equity, Inclusion and Accessibility

Obesity and metabolic disease have high prevalence (>50%) in our Boston Medical Center population and are associated with worse outcomes, including early treatment failure and recurrence for breast cancer, prostate cancer and a number of other solid tumors associated with obesity. My work on Bromodomain and ExtraTerminal (BET) protein regulation of cancer progression in obesity has brought me into close contact with cancer disparities and health equity concerns.

Specifically, our knowledge base that informs and refines the medical oncology standard of care for these tumor types has generally been built on clinical trials with patients without metabolic comorbidities. We do not know if treatment decisions are properly justified for diverse patient populations where the prevalence of these comorbidities is high. Health equity concerns are at the core of basic research questions into why patients, such as African American women with triple negative breast cancer and co-morbid obesity-driven diabetes, are likely not receiving optimal treatment in the U.S. health care system. This theme is a central motivator for my work and has played a deepening role in the clinical translational experiments I am developing with Boston Medical Center collaborators.

Although I am a health disparities researcher and advocate for cancer disparities, one of my most meaningful public speaking engagements was in a church basement in Salem, MA on a snowy January evening. I presented histopathology slides of normal bone marrow and leukemic bone marrow to a lay audience of about 15 members of the local community. When audience members’ hands shot up to ask earnest questions, some with urgency to understand the clinical and biological implications of the histology, I realized the widespread hunger for compassionate expert opinion, reassurance, education and partnership with our cancer patients and their families. Questions of trust and doubt swirl around a cancer diagnosis, and I think that our mission as researchers, clinicians and public health advocates must be informed first by this fact.

The Boston neighborhoods that experienced high COVID19 mortality are the same neighborhoods where screening for lung, prostate and colorectal cancer are low, and closely overlap with food deserts, obesity and diabetes. It is no accident that these same streets were subject to historic red-lining, emphasizing the pervasive impact of structural racism on cancer outcomes, not only in Boston but in every region of the United States.

My work with underserved patients at Boston Medical Center have catalyzed my focus on the mechanisms behind race-based cancer disparities. The current models to understand risks for cancer incidence, progression, treatment failure and recurrence are not well designed to meet the needs of Black women with breast cancer or Black men with prostate cancer. For example, data reveal that Oncotype scores for Black women under-estimate risk for progression of ER+, node-negative breast cancer. In retrospect, this disappointment is unsurprising because the models are built on metabolically healthy white women and fail to account fully for metabolic and obesity co-morbidities that disproportionately affect Black women. Innovative modeling of the tumor microenvironment and analysis of BET protein mechanism that likely drives some of these differences will suggest new avenues for clinical trials for breast cancer progression. The impact of our approach will be to bring cardiometabolic variables to inform to clinical decision making in breast oncology.

Similarly, recent work is revealing that prostate cancer patients with obesity and diabetes have very different biology in the tumor microenvironment, compared to patients with the same prostate cancer stage, who are otherwise metabolically normal. Metabolic biomarkers do not yet inform prostate oncology practice and Black men (who bear a greater burden of obesity and diabetes than European American men) are uniquely underserved. Research, both basic and clinical-translational, at Boston Medical Center where our ~50% representation of Black men with prostate cancer is much higher than at neighboring hospitals in Boston or elsewhere in New England, is an ideal location for cancer disparities work to make a difference for needful patients.

Professor
Boston University Chobanian & Avedisian School of Medicine
Pharmacology, Physiology & Biophysics


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 Chobanian & Avedisian 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
5U01CA243004-04

Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer
08/07/2018 - 07/31/2024 (PI)
NIH/National Cancer Institute
5R01CA222170-05

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
2023 Multiscale analysis of metabolic inflammation as a driver of breast cancer 5U01CA243004-04
2022 Multiscale analysis of metabolic inflammation as a driver of breast cancer 5U01CA243004-03
2022 Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer 5R01CA222170-05
2021 Multiscale analysis of metabolic inflammation as a driver of breast cancer 5U01CA243004-02
2021 Mechanisms of BET bromodomain metabolic reprogramming in triple negative breast cancer 5R01CA222170-04 2
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
Showing 10 of 36 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. Mori JO, Elhussin I, Brennen WN, Graham MK, Lotan TL, Yates CC, De Marzo AM, Denmeade SR, Yegnasubramanian S, Nelson WG, Denis GV, Platz EA, Meeker AK, Heaphy CM. Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer. Nat Rev Urol. 2024 May; 21(5):258-273.View Related Profiles. PMID: 37907729
     
  2. Adler FR, Anderson ARA, Bhushan A, Bogdan P, Bravo-Cordero JJ, Brock A, Chen Y, Cukierman E, DelGiorno KE, Denis GV, Ferrall-Fairbanks MC, Gartner ZJ, Germain RN, Gordon DM, Hunter G, Jolly MK, Karacosta LG, Mythreye K, Katira P, Kulkarni RP, Kutys ML, Lander AD, Laughney AM, Levine H, Lou E, Lowenstein PR, Masters KS, Pe'er D, Peyton SR, Platt MO, Purvis JE, Quon G, Richer JK, Riddle NC, Rodriguez A, Snyder JC, Lee Szeto G, Tomlin CJ, Yanai I, Zervantonakis IK, Dueck H. Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation. Cell Syst. 2023 Apr 19; 14(4):252-257. PMID: 37080161; PMCID: PMC10760508; DOI: 10.1016/j.cels.2023.03.002;
     
  3. Paul I, Bolzan D, Youssef A, Gagnon KA, Hook H, Karemore G, Oliphant MUJ, Lin W, Liu Q, Phanse S, White C, Padhorny D, Kotelnikov S, Chen CS, Hu P, Denis GV, Kozakov D, Raught B, Siggers T, Wuchty S, Muthuswamy SK, Emili A. Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT. Nat Commun. 2023 Feb 08; 14(1):688.View Related Profiles. PMID: 36755019; PMCID: PMC9908882; DOI: 10.1038/s41467-023-36122-x;
     
  4. Wang Y, Huang J, Ang TFA, Zhu Y, Tao Q, Mez J, Alosco M, Denis GV, Belkina A, Gurnani A, Ross M, Gong B, Han J, Lunetta KL, Stein TD, Au R, Farrer LA, Zhang X, Qiu WQ. Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer's Disease. medRxiv. 2023 Jan 18.View Related Profiles. PMID: 36711847; PMCID: PMC9882408; DOI: 10.1101/2023.01.16.23284571;
     
  5. Samuels L, Boskov N, Francisco Oliveira A, Sun E, Starobinski D, Trachtenberg A, Monga M, Varia M, Canetti R, Devaiah A, Denis GV. Automated Exposure Notification for COVID-19. J Young Investig. 2022 Dec; 25(12).View Related Profiles. PMID: 37408595; PMCID: PMC10321550
     
  6. Ennis CS, Llevenes P, Qiu Y, Dries R, Denis GV. The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities. Front Endocrinol (Lausanne). 2022; 13:1044670.View Related Profiles. PMID: 36531496; PMCID: PMC9751481; DOI: 10.3389/fendo.2022.1044670;
     
  7. Jafari N, Chen A, Kolla M, Pompa IR, Qiu Y, Yu R, Llevenes P, Ennis CS, Mori J, Mahdaviani K, Halpin M, Gignac GA, Heaphy CM, Monti S, Denis GV. Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease. Adv Cancer Biol Metastasis. 2022 Dec; 6.View Related Profiles. PMID: 36644690; PMCID: PMC9836031; DOI: 10.1016/j.adcanc.2022.100073;
     
  8. Jafari N, Llevenes P, Denis GV. Exosomes as novel biomarkers in metabolic disease and obesity-related cancers. Nat Rev Endocrinol. 2022 Jun; 18(6):327-328.View Related Profiles. PMID: 35361917; PMCID: PMC9152991; DOI: 10.1038/s41574-022-00666-7;
     
  9. Sergesketter AR, Geng Y, Shammas RL, Denis GV, Bachelder R, Hollenbeck ST. The Association Between Metabolic Derangement and Wound Complications in Elective Plastic Surgery. J Surg Res. 2022 Oct; 278:39-48. PMID: 35588573; PMCID: PMC9329200; DOI: 10.1016/j.jss.2022.03.017;
     
  10. Alhousami T, Diny M, Ali F, Shin J, Kumar G, Kumar V, Campbell JD, Noonan V, Hanna GJ, Denis GV, Monti S, Kukuruzinska MA, Varelas X, Bais MV. Inhibition of LSD1 Attenuates Oral Cancer Development and Promotes Therapeutic Efficacy of Immune Checkpoint Blockade and YAP/TAZ Inhibition. Mol Cancer Res. 2022 May 04; 20(5):712-721.View Related Profiles. PMID: 35105672; PMCID: PMC9081163; DOI: 10.1158/1541-7786.MCR-21-0310;
     
Showing 10 of 75 results. Show More

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

Bar chart showing 75 publications over 27 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
20212
20227
20234
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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