The main focus of our research is to understand the molecular basis of therapy resistance in multiple cancer types including in prostate, breast, and colon cancers. To accomplish our goals, we are investigating two different, but complementary projects. The first project delineates how mitochondria-mediated cell death signaling is defective in cancer cells and cancer stem cells.
The second project defines the role of heat-shock proteins in cancer cell survival and death. We are also characterizing the role of mitochondria in health disparities among prostate and breast cancer patients. Our research suggests that protein complexes are important regulators of cancer cell death and survival. We use multiple biochemical, genetic, cellular, and molecular approaches to identify and characterize protein complexes in subcellular compartments including in the mitochondrion. Detailed understanding of protein complexes will lay a foundation for targeting cell death and survival machinery for cancer therapy. Our model system includes both laboratory cell culture and mouse model of cancer to examine cellular signaling in response to anticancer agents as well as phytochemicals. Our ultimate goal is to target mitochondria and cell death for prevention and therapy of multiple types of cancer.
The National Cancer Institute, American Cancer Society, and Department of Defense support our research.
Yadav, N., Pliss, A., Kuzmin, A., Rapali, P., Sun, L., Prasad, P., and Chandra, D. (2014). Transformations of the macromolecular landscape at mitochondria during apoptotic cell death. Cell Death & Disease, 5, e1453.
Koochekpour, S., Marlowe T., Singh, K., Kristopher, A., and Chandra, D. (2013). Reduced mitochondrial DNA (mtDNA) content associates with poor prognosis of prostate cancer in African American men. PLoS ONE, 8 (9), e74688.
Gogada, R., Yadav N., Liu, J.W., Tang, S-H., Zhang, D., Schneider, A., Seshadri, A., Sun, L., Aldaz, C.M., Tang, D.G., and Chandra, D. (2013). Bim, a proapoptotic protein, upregulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer. Journal of Biological Chemistry, 288, 368-381 (Faculty of 1000 Biology Paper).
Gogada, R., Prabhu, V., Amadori, M., Scott, R., Hashmi, S., and Chandra, D. (2011). Resveratrol induces p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated Bax protein oligomerization on mitochondria to initiate cytochrome c release and caspase activation. Journal of Biological Chemistry, 286, 28749-28760.
Jeter, C.R., Badeaux, M., Choy, G., Chandra, D., Patrawala, L., Liu, C., Calhoun-Davis, C., Zaehres, H., Daley, G.Q., Tang, D.G. (2009). Functional Evidence that the Self-Renewal Gene NANOG Regulates Human Tumor Development (p N/A) . Stem Cells, 27, 993-1005.
Chandra D, Choy G, and Tang DG. (2007). Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release: evidence that its pro-apoptotic or pro-survival functions involve differential interactions with caspase-3. Journal of Biological Chemistry, 282, 31289-301.
Chandra*, D., Bratton, S.B., Person, M.D., Tian, Y., Martin, A.G., Ayres, M., Fearnhead, H.W., Gandhi, V., and Tang*, D.G. (2006). Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome c and inhibiting apoptosome. Cell, 125, 1333-1346. * Co-corresponding Authors