|SOM Address||Room 145, Cancer Research Building I|
Research in our lab is focused in the following areas:
- Investigating the molecular links between obesity and cancer, emphasizing aspects that have potential clinical significance and development of novel therapeutics. Using various physiologically relevant mouse models and cell lines, our aim is to find molecular targets that can be effectively targeted by small molecule inhibitors as well as bioactive food components. Our overall goal is to understand the molecular networks by which obesity affects stem cells, epithelial-mesenchymal transition and metastatic progression of breast carcinogenesis and discover novel agents to effectively disrupt obesity-cancer axis.
- 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.
- Development of novel cancer prevention strategies using bioactive compounds.
- Taliaferro-Smith, L., Nagalingam, A., Knight, B. B., Oberlick, E., Saxena, N. K., and Sharma, D. Integral role of PTP1B in adiponectin mediated inhibition of oncogenic actions of leptin in breast carcinogenesis. Neoplasia, 15(1):23-38, 2013.
- Yan, D., Avtanski, D., Saxena, N. K., and Sharma, D. Leptin-induced Epithelial-Mesenchymal Transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. Journal of Biological Chemistry, 287(11):8598-8612, 2012.
- Nagalingam, A., Arbiser, J. L., Saxena, N. K., and Sharma, D. Honokiol activates AMP-activated protein kinase in breast cancer cells via LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Research, 14(1):R35, 2012.
- Nagalingam, A., Tighiouart, M., Ryden, L., Joseph, L., Landberg, G., Saxena, N. K., and Sharma, D. Med1 plays a critical role in the development of tamoxifen resistance. Carcinogenesis, 33(4):918-930, 2012.
- 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., 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.
- 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.
- 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.
- 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.