Breast Cancer, Obesity-Cancer Connection, Adipocytokines, Metastasis, Tamoxifen Resistance, Novel Therapeutics, Bioactive Food Components, Signaling Mechanisms
Associate Professor of Oncology
M.S., University of Delhi, India Ph.D., University of Delhi, School of Biotechnology, Jawaharlal Nehru University, Delhi, India
Fellow, Molecular Biology, University of Maryland, Baltimore, MD
Fellow, Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
breast cancer research
breast cancer and obesity
The research in Sharma lab is focused in two main areas: 1) Investigating the molecular links between obesity and cancer, emphasizing aspects that have potential clinical significance and development of novel therapeutics. To get to the bottom of obesity-cancer connection, her lab is exploring the genes, molecules, hormones and cellular processes that could cause and promote cancer in obese people. Using various physiologically relevant mouse models and cell lines, their aim is to find molecular targets that can be effectively targeted by small molecule inhibitors as well as bioactive food components. Their overall goal is to understand the molecular networks by which obesity affects carcinogenesis and discover novel agents to effectively disrupt obesity-cancer axis. 2) Investigating the molecular mechanisms by which breast cancers acquire resistance to endocrine therapy and develop new treatment strategies to overcome this resistance. In this research, they combine molecular and genetic approaches to focus on the crosstalk between growth factor pathways and coregulator proteins. The goal is to understand the mechanistic links, define molecular profiles that can be used to predict development of endocrine resistance and develop targeted therapies.
Sharma, D., and Fondell, J. D. Temporal formation of distinct thyroid hormone receptor coactivator complexes in HeLa cells. Mol. Endocrinol., 14(12): 2001- 2009, 2000.
Sharma, D., and Fondell, J. D. Ordered recruitment of histone aceyltransferases and TRAP/Mediator complex to thyroid hormone responsive promoters in vivo. Proc. Natl. Acad. Sci., USA, 99(12): 7934-7939, 2002.
Wang, Q., Sharma, D., Ren, Y. and Fondell, J. D. A coregulatory role for the TRAP/ Mediator complex in androgen receptor mediated receptor mediated gene expression. J. Biol. Chem., 277(45): 42852-42858, 2002.
Sharma, D., and Vertino, P.M. Epigenetic Regulation of MDR1 Gene in Breast Cancer: CpG Methylation Status Dominates the Stable Maintenance of a Silent Gene. Cancer Biol Ther. 3(6):549-50, 2004.
Sharma, D., Blum, J., Yang, X., Beaulieu, N., Macleod, A. R., and Davidson, N. E. Release of Methyl CpG Binding Proteins and Histone Deacetylase 1 from the Estrogen Receptor Alpha (ER) Promoter upon Reactivation in ER-negative Human Breast Cancer Cells. Mol Endocrinol., 19 (7): 1740-1751, 2005.
Pandey, P. K., Udayakumar, T. S., Lin, X., Sharma, D., Shapiro, P. S., and Fondell, J. D. Activation of TRAP/mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. Mol. Cell. Biol., 25(24): 10695-10710, 2005.
Sharma, D., Saxena, N. K., Vertino, P. M., and Anania, F. A. Leptin mediates a proliferative response in human endometrial cancer cells by activating multiple signal transduction pathways. Endocrine Related Cancer, 13(2): 629-640, 2006.
Sharma, D., Saxena, N. K., Davidson, N. E., and Vertino, P. M. Restoration of tamoxifen sensitivity in ER-negative breast cancer cells. Tamoxifen-bound reactivated estrogen receptor recruits distinct chromatin modifying corepressors complexes. Cancer Research, 66: 6370-6378, 2006.
Saxena, N. K., Sharma, D., Ding, X., Lin, S., Marra, F., Merlin, D., and Anania, F. A. Concomitant activation of the JAK/STAT, PI3K/AKT and ERK signaling is involved in leptin mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Research, 67: 2497-2507, 2007.
Saxena, N. K., Vertino, P. M., Anania, F. A., and Sharma, D.. Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyl transferases and mediator complex to cyclin D1 promoter via STAT3. JBC, 282: 13316-13325, 2007.
Subramanian, K., Jia, D., Kapoor-Vazirani, P., Powell, D. R., Collins, R. E., Sharma, D., Peng, J., Cheng, X., and Vertino, P. M. Regulation of the Estrogen receptor alpha by the SET7 lysine methyltransferases. Molecular Cell, 30(3): 336-347, 2008.
Saxena, N. K., Taliaferro-Smith, L., Brandon, B., Merlin, D., Anania, F. A., O'Regan, R. M., and Sharma, D. Bidirectional crosstalk between leptin and IGF1 signaling transactivates epidermal growth factor receptor and promotes invasion and migration of breast cancer cells. Cancer Research, 68(23): 9712-9722, 2008.
Taliaferro-Smith, L., Nagalingam, A., Zhong, D., Zhou, W., Saxena, N. K., and Sharma, D. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of metastatic properties of breast cancer cells. Oncogene, 28(29):2621-2633, 2009.
Graham, T. R., Yacoub, R., Taliaferro-Smith, L., Osunkoya, A., Odero-Marah, V. A., Liu, T., Kimbro, S. K., Sharma, D., and O'Regan, R. M. Reciprocal regulation of ZEB1 and AR in triple negative breast cancer cells. Breast Cancer Research and Treatment, 123(1):139-147, 2010.
Saxena, N. K., and Sharma, D. Metastasis suppression by adiponectin: LKB1 rises up to the challenge. Cell Adhesion and Migration, 4(3): 358-362, 2010.
Saxena, N. K., Fu, P. P., Nagalingam, A., Wang, J., Handy, J., Cohen, C., Tighiouart, M., Sharma, D., and Anania, F. A. Adiponectin modulates c-Jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma. Gastroenterology, 139(5): 1762-1773, 2010.
Sharma, D., Wang, J., Fu, P. P., Sharma, S., Nagalingam, A., Mells, J., Handy, J., Page, A. J., Cohen, C., Anania, F. A., and Saxena, N. K. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Hepatology, 52(5): 1713-1722, 2010.
Saxena, N. K., and Sharma, D. Epigenetic Reactivation of Estrogen Receptor: Promising tools for restoring response to endocrine therapy. Molecular and Cellular Pharmacology, 2(5): 191-202, 2010.
Kim, S. H., Nagalingam, A., Saxena, N. K., Singh, S. V., and Sharma, D. Benzyl isothiocyanate inhibits oncogenic actions of leptin in human breast cancer cells by suppressing activation of signal transducer and activator of transcription 3. Carcinogenesis, 32(3): 359-367, 2011.
Nagaraju, G. P. C. and Sharma, D. Anticancer role of SPARC, an inhibitor of adipogenesis. Cancer Treatment Reviews, 2011 Jan 13 [Epub ahead of print].
Knight, B. B., Oprea-Illies, G. M., Nagalingam, A., Yang, L., Cohen, C., Saxena, N. K., and Sharma, D. Survivin upregulation, dependent on leptin-EGFR-Notch axis, is essential for leptin induced migration of breast carcinoma cells. Endocrine Related Cancer, 2011 May 9 [Epub ahead of print].