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Search Results to Gerald V. Denis, PhD

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Research Expertise & Professional Interests 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.
Self-Described Keywords Prostate Cancer
Self-Described Keywords immunology
Self-Described Keywords cancer disparities

One or more keywords matched the following items that are connected to Denis, Gerald

Item TypeName
Concept Breast Neoplasms
Concept Neoplasms
Concept Neoplasms, Radiation-Induced
Concept Thymus Neoplasms
Concept Early Detection of Cancer
Academic Article Apoptosis during the development of radiogenic thymic lymphomas: effects of treatments inhibiting lymphoma development.
Academic Article Telomere homolog oligonucleotides induce apoptosis in malignant but not in normal lymphoid cells: mechanism and therapeutic potential.
Academic Article Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation.
Academic Article Parallel imaging microfluidic cytometer.
Academic Article BET domain co-regulators in obesity, inflammation and cancer.
Academic Article Healthy obese persons: how can they be identified and do metabolic profiles stratify risk?
Academic Article Metabolic health reduces risk of obesity-related cancer in framingham study adults.
Academic Article Barriers to Obtaining Sera and Tissue Specimens of African-American Women for the Advancement of Cancer Research.
Academic Article Clinical trials for BET inhibitors run ahead of the science.
Academic Article Associations between metabolic disorders and risk of cancer in Danish men and women--a nationwide cohort study.
Academic Article Correction to "Barriers to Obtaining Sera and Tissue Specimens of African-American Women for the Advancement of Cancer Research".
Academic Article BRD4 Regulates Breast Cancer Dissemination through Jagged1/Notch1 Signaling.
Academic Article Energy Balance and Cancer. A. J. Dannenberg, N. A. Berger, Eds
Academic Article Diabetes and breast cancer mortality in Black women.
Academic Article BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer.
Academic Article Impact of Energy Balance on Cancer Disparities. In "Energy Balance and Cancer". D.J. Bowen, G. V. Denis, N. A. Berger, Eds
Academic Article "Obesity-Associated" Breast Cancer in Lean Women: Metabolism and Inflammation as Critical Modifiers of Risk.
Academic Article Type II Diabetes and Incidence of Estrogen Receptor Negative Breast Cancer in African American Women.
Academic Article BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition.
Academic Article BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment.
Academic Article BRD4 regulates metastatic potential of castration-resistant prostate cancer through AHNAK.

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  • Cancer
  • Immunology