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

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



All of the work in my lab is focused on the study of a novel transcriptional co-activator, the double bromodomain protein Brd2, which I discovered as a postdoc (Denis & Green 1996 Genes Dev. 10). This protein is related to the basal transcription factor TAFII250; Brd2 binds to acetylated histones through its bromodomains, then recruits transcription factors and co-activators/co-repressors to promoter chromatin. Through its association with the SWI/SNF complex, Brd2 helps remodel chromatin to regulate transcription activity (Denis et al. 2000 Cell Growth Diff. 11; Guo et al. 2000 J. Cell Sci. 113; Denis et al. 2006 J. Proteome Res. 5). This highly conserved and ubiquitous protein is essential for life; knockout of the gene is lethal in all organisms tested so far (mice, Drosophila, yeast). We have used American Cancer Society and NCI funding to discover that, in mammals, two key targets of Brd2 are the cyclin A locus (Sinha et al. 2005 Biochem. J. 387), which controls cell cycle progression through S phase, and gene targets of the PPARgamma transcription factor, which controls adipogenic transcription. Brd2 is a positive regulator of proliferation but a negative regulator of adipogenesis. In transgenic mice that constitutively express Brd2 in B cells, cyclin A is upregulated and the cell cycle is destabilized, leading to an aggressive non-Hodgkin’s lymphoma (Greenwald et al. 2004 Blood 103). We are using new funding from the NCI to develop novel transcriptional and proteomic profiling of this and related human malignancies, as well as to identify new drug targets and develop original therapeutic approaches for its treatment (Longe et al. 2005 Blood 106; Lenburg et al. 2007 J. Biol. Chem. 282; Longe et al. 2007 Proc. Am. Assoc. Cancer Res. 2007; Longe et al. 2008 Int. J. Cancer; Romesser et al. 2008. Am. J. Pathol.). Meanwhile, whole-animal knockdown of Brd2 in mice causes extreme, morbid obesity; dramatically illustrating an unexpected role for Brd2 in energy homeostasis. With new, pilot funding from the Boston Area Diabetes and Endocrinology Research Center, we have shown that brd2 knockdown mice are hyperinsulinemic, yet never become diabetic, and exhibit hypoglycemia and better glucose tolerance than wild type. Furthermore, Brd2 associates with PPARgamma and alters adipogenesis from 3T3-L1 pre-adipocytes; Brd2 opposes PPARgamma transcriptional activation, suggesting Brd2 plays a novel, crucial negative regulatory role in adipogenesis (Wang et al. 2008 Genes Dev.). Finally, we have recently reconstituted the murine immune system with hematopoietic stem cells transduced with lentiviruses for Brd2 overexpression or shRNA knockdown, and learned that Brd2 expression causes a dramatic expansion of the lymphoid compartment and B cell hypersensitivity to mitogens, nicely recapitulating the transgenic model, whereas Brd2 knockdown completely blocks lymphoid development, suggesting that this factor plays a crucial and fundamental role in normal immune biology and the processes of adaptive immunity.

Associate Professor
Boston University School of Medicine
Pharmacology & Experimental Therapeutics


Center Faculty Member
Boston University School of Medicine
Cancer Research Center


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




Uncoupling obesity from breast cancer in African American women
09/01/2016 - 08/31/2018 (PI)
NIH/National Cancer Institute
4U01CA182898-04

Uncoupling Obesity from Breast Cancer in African American Women
09/24/2013 - 08/31/2016 (PI)
NIH/National Cancer Institute
5U01CA182898-03

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

Mechanisms of Brd2 Immunoprotection for Insulin Resistance
09/30/2011 - 08/31/2013 (PI)
NIH/National Diabetes & Digestive & Kidn
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

Biomarkers for Lymphoma in a New Transgenic Mouse Model
03/01/2004 - 02/28/2006 (PI)
NIH/National Cancer Institute
5 R03 CA102889 02

A Novel, Inducible Nuclear Kinase Linked to Leukemia
09/15/1997 - 09/29/2002 (PI)
NIH/National Cancer Institute
5 R29 CA75107 05




Yr Title Project-Sub Proj Pubs
2017 Uncoupling obesity from breast cancer in African American women 5U01CA182898-05 12
2016 Uncoupling obesity from breast cancer in African American women 4U01CA182898-04 12
2015 Uncoupling obesity from breast cancer in African American women 5U01CA182898-03 12
2015 Uncoupling obesity from breast cancer in African American women 3U01CA182898-02S1 12
2014 Uncoupling obesity from breast cancer in African American women 5U01CA182898-02 12
2013 Uncoupling obesity from breast cancer in African American women 1U01CA182898-01 12
2011 Mechanisms of Brd2 immunoprotection from insulin resistance 1R56DK090455-01A1 13
2010 BRD2-MULTIPROTEIN COMPLEXES IN MAMMALIAN CELL CYCLE TRANSCRIPTIONAL CONTROL 5P41RR010888-14-6783 236
2009 BRD2-MULTIPROTEIN COMPLEXES IN MAMMALIAN CELL CYCLE TRANSCRIPTIONAL CONTROL 5P41RR010888-13-6129 236
2008 BRD2-MULTIPROTEIN COMPLEXES IN MAMMALIAN CELL CYCLE TRANSCRIPTIONAL CONTROL 5P41RR010888-12-5184 236
Showing 10 of 27 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.

  1. 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.
  2. 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.
  3. 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.View Related Profiles. PMID: 28408379; DOI: 10.1158/1940-6207.CAPR-17-0083;.
  4. 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.View Related Profiles. PMID: 27995352; DOI: 10.1007/s10552-016-0837-z;.
  5. 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; DOI: 10.1158/0008-5472.CAN-16-0559;.
  6. 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.View Related Profiles. PMID: 27695380.
  7. 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.View Related Profiles. PMID: 27491296; DOI: 10.1007/s00018-016-2320-0;.
  8. 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.View Related Profiles. PMID: 27769357; DOI: 10.1016/j.ddtec.2016.06.004;.
  9. 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.View Related Profiles. PMID: 27441007; DOI: 10.4137/CMWH.S34698;.
  10. 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.View Related Profiles. PMID: 27008626; PMCID: PMC4805167; DOI: 10.1371/journal.pone.0151329;.
Showing 10 of 54 results. Show More

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

Bar chart showing 54 publications over 21 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
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

cell cycle
hematologic malignancy
immunology
inflammation
mouse models
obesity
stem cells
tumor suppressors
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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