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The emergence of important critical opinion and new research about this protected phenotype is leading to a reassessment of cardiometabolic and cancer risks. These relatively healthy but obese humans appear to bend the rules of metabolism.

Denis & Bowen 2013 Chapter

Denis and Hamilton 2013

Denis and Obin 2012

Reduced expression of the BET protein Brd2 inhibits inflammation and reveals mechanistic links between obesity, metabolism, inflammation and cancer:

Belkina et al 2013 – JI

Belkina et al 2013 – JLB

Wang, Deeney & Denis 2013


This new field has been generating significant excitement. Immunometabolism is arguably one of the most important new directions in obesity and type 2 diabetes research. The field was launched on the demonstration that both diseases are characterized by chronic inflammation, and that prevention of immune cell-mediated inflammation prevents the development of insulin resistance in animal models of obesity. Furthermore, obese individuals with hallmarks of chronic inflammation are more likely to become insulin resistant, which indicates that inflammation is critical for the development of metabolic imbalance in humans. Inflammation is also linked to many diabetic complications, whose cost to both individuals and the health care system is steep. Overall, these findings suggest that use of available immune system-targeting drugs that moderate inflammation may have efficacy in stemming the explosive global increase in type 2 diabetes. A more comprehensive understanding of the roles of immune cells and immune-mediated inflammation in obesity and type 2 diabetes will assess the potential of harnessing the power of immunomodulatory drugs for the fight against metabolic disease.

Nikolajczyk et al 2012


Belkina and Denis, 2012

A new hypothesis that many inflammatory diseases, including cancer and Type 2 diabetes, have a common epigenetic foundation.
Denis (2010). Discovery Med 10(55): 489-499.

Major significance of the Brd2 hypomorphic phenotype for obesity and Type 2 diabetes.
Belkina & Denis (2010). Curr Opin Endocrinol Diabetes Obes 17(5): 472-477.

New mechanisms of transcriptional co-activation in adipogenesis and energy metabolism.

Denis, Nikolajczyk & Schnitzler (2010). FEBS Lett 584(15): 3260-3268.


1.  Whole-body reduction of Brd2 levels in mice leads to the very surprising result that mice become extremely obese, yet are preserved from insulin resistance and Type 2 diabetes.

Wang F., H. Liu, W. P. Blanton, A. Belkina, N. K. LeBrasseur and G. V. Denis (2010). Brd2 disruption in mice causes severe obesity without Type 2 diabetes. Biochem. J. 425: 71 – 83. PMID: 19883376

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2. Bromodomain protein Brd2-driven B cell malignancy in a mouse model.

Greenwald R., J. R. Tumang, A. Sinha, N. Currier, R. D. Cardiff, T. L. Rothstein, D. V. Faller and G. V. Denis (2004). Eμ-BRD2 transgenic mice develop B cell lymphoma and leukemia. Blood 103: 1475 – 1484. PMID: 14563639

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3. Bromodomain analysis of cyclin A transcription.

Sinha, A., D. V. Faller and G. V. Denis (2005). Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A. Biochem. J. 387: 257 – 269.
PMID: 15548137; PMC: 1134954

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4. MALDI and LC-MS/MS identification of Brd2 multiprotein complexes.

Denis, G. V., M. E. McComb, D. V. Faller, A. Sinha, P. B. Romesser and C. E. Costello (2006). Identification of transcription complexes that contain the double bromodomain protein Brd2 and chromatin remodeling machines. J. Proteome Res. 5: 502 – 511. PMID: 16512664; PMC: 2823066

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5. Genome-wide transcriptional and proteomic profiling reveal a malignancy signature of diffuse large B cell lymphoma.

Lenburg, M., A. Sinha, D. V. Faller and G. V. Denis (2007). Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis. J. Biol. Chem. 282: 4803 – 4811. PMID: 17166848; PMC: 2819333

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Romesser, P. B., D. H. Perlman, D. V. Faller, C. E. Costello, M. E. McComb and G. V. Denis (2009). Development of a malignancy-associated proteomic signature for diffuse large B cell lymphoma. Am. J. Pathol. 175: 25–35. PMID: 19498000; PMC: 2708791

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6. Therapeutics for leukemia and lymphoma.

Denis, G. V. (2007). Imatinib mesylate (Gleevec) and the emergence of chemotherapeutic drug-resistant mutations. In H. L. Kaufman, S. Wadler and K. H. Antman, Eds., Cancer Drug Discovery and Development; Specific Drugs for Molecular Targeting in Oncology,, Part IV, Chapter 22. Humana Press; Totowa, NJ. In press.

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Longe, H., P. B. Romesser, A. Rankin, D. V. Faller, M. S. Eller, B. A. Gilchrest and G. V. Denis (2009). Telomere homolog oligonucleotides induce apoptosis in malignant but not in normal lymphoid cells: Mechanism and therapeutic potential. Int. J. Cancer. 124:473–482. PMID: 19003960

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Primary teaching affiliate
of BU School of Medicine