Special Interests:Heat shock protein regulation of cancer cell death and survival Mitochondrial regulation of cell death in cancer Oxidative phosphorylation and reactive oxygen species Cancer health disparities Anticancer therapeutics and phytochemicals
About Dhyan Chandra
Roswell Park Comprehensive Cancer Center
- Associate Professor of Oncology
- Department of Pharmacology & Therapeutics
- Member, PhD Program in Cancer Sciences, Experimental Therapeutics Track
- Member, Developmental Therapeutics of CCSG (Comprehensive Cancer Center Support Grant) program
- Member, Breast, Lung, Genitourinary, and Gastrointestinal TRGs (Translational Research Groups)
Education and Training:
- PhD - School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
- Postdoctoral - University of Texas MD Anderson Cancer Center, Smithville, Texas
The main focus of our research is to define the role of mitochondrial biology in cancer and understand the molecular basis of therapeutic resistance in multiple types of cancer including in prostate, pancreatic, breast, and colon cancers. We are working on several interconnected and complementary research 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 mitochondrial unfolded protein response in cancer progression and the development of therapeutic resistance in patients with cancer. The third project characterizes the role of mitochondria in cancer health disparities among Americans. We also investigate the role of mitochondrial dysfunction in age-related neurodegenerative diseases and drug abuse. Our research suggests that deregulation of protein complexes contributes to tumor progression and therapeutic resistance in cancer. We use multiple biochemical, genetic, cellular, mouse models of cancer, clinical, and molecular approaches to identify and characterize protein complexes in subcellular compartments including in mitochondria. We envision that a detailed understanding of protein complexes will lay a foundation for targeting cell death and survival machineries for better therapeutic outcomes in patients with cancer. Our ultimate goals are to understand the mitochondrial biology and identify novel targets for prevention and therapy of multiple types of cancer as well as for other age-related diseases.
Featured on Cancer Talk
- O’Malley J, Kumar R, Inigo J, Yadava N, and Chandra D. Mitochondrial Stress Response and Cancer. Trends in Cancer. 2020 (in press).
- Kumar S, O'Malley J, Chaudhary AK, Inigo JR, Yadav N, Kumar R, Chandra D. Hsp60 and IL-8 axis promotes apoptosis resistance in cancer. Br J Cancer. 2019 Nov;121(11):934-943. doi: 10.1038/s41416-019-0617-0. Epub 2019 Nov 1. PMID: 31673102; PMCID: PMC6889399.
- Kumar R, Bhat TA, Walsh EM, Chaudhary AK, O'Malley J, Rhim JS, Wang J, Morrison CD, Attwood K, Bshara W, Mohler JL, Yadav N, Chandra D. Cytochrome c Deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer. Cancer Res. 2019 Apr 1;79(7):1353-1368. doi:10.1158/0008-5472.CAN-18-2383. Epub 2019 Feb 14. PMID: 30765600; PMCID: PMC6445777.
- O'Malley J, Kumar R, Kuzmin AN, Pliss A, Yadav N, Balachandar S, Wang J, Attwood K, Prasad PN, Chandra D. Lipid quantification by Raman microspectroscopy as a potential biomarker in prostate cancer. Cancer Lett. 2017 Jul 1;397:52-60. doi: 10.1016/j.canlet.2017.03.025. Epub 2017 Mar 23. PMID: 28342983; PMCID: PMC5449194.
- Yadav N, Kumar S, Marlowe T, Chaudhary AK, Kumar R, Wang J, O'Malley J, Boland PM, Jayanthi S, Kumar TK, Yadava N, Chandra D. Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents. Cell Death Dis. 2015 Nov 5;6:e1969. doi: 10.1038/cddis.2015.305. PMID: 26539916; PMCID: PMC4670921.
- Koochekpour S, Marlowe T, Singh KK, Attwood K, Chandra D. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men. PLoS One. 2013 Sep 23;8(9):e74688. doi: 10.1371/journal.pone.0074688. eCollection 2013. PMID: 24086362; PMCID: PMC3781126.
- Gogada R, Yadav N, Liu J, Tang S, Zhang D, Schneider A, Seshadri A, Sun L, Aldaz CM, Tang DG, Chandra D. Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer. J Biol Chem. 2013 Jan 4;288(1):368-81. doi: 10.1074/jbc.M112.386102. Epub 2012 Nov 14. PMID: 23152504; PMCID: PMC3537034.
- Gogada R, Prabhu V, Amadori M, Scott R, Hashmi S, Chandra D. 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. J Biol Chem. 2011 Aug 19;286(33):28749-60. doi: 10.1074/jbc.M110.202440. Epub 2011 Jun 28. PMID: 21712378; PMCID: PMC3190683.
- Chandra D, Choy G, Tang DG. 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. J Biol Chem. 2007 Oct 26;282(43):31289-301. Epub 2007 Sep 6. PMID: 17823127.
- Chandra D*, Bratton SB, Person MD, Tian Y, Martin AG, Ayres M, Fearnhead HO, Gandhi V, Tang DG*. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome C and inhibiting apoptosome. Cell. 2006 Jun 30;125(7):1333-46. PMID: 16814719. *Corresponding authors.
- Chandra D, Choy G, Deng X, Bhatia B, Daniel P, Tang DG. Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death. Mol Cell Biol. 2004 Aug;24(15):6592-607. PMID: 15254227; PMCID: PMC444870.