Research 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
- 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 defines the role of mitochondrial unfolded protein response in cancer progression and development of therapeutic resistance in cancer patients. The second project delineates how mitochondria-mediated cell death signaling is defective in cancer cells and cancer stem cells. The third project characterizes the role of mitochondria in cancer health disparities among Americans. We also investigating 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 detailed understanding of protein complexes will lay a foundation for targeting mitochondria, cell death, and survival machineries for better therapeutic outcomes in cancer patients. Our ultimate goals are to understand the mitochondrial biology and identify novel targets for prevention and treatment of multiple types of cancer as well as other age-related diseases.
Featured on Cancer Talk
- Kumar R, Chaudhary AK, Inigo JR, Woytash J, Gokhale AA, Bshara W, Attwood K, Wang J, Spernyak J, Rath E, Yadav N, Haller D, Goodrich DW, Tang DG, and Chandra D. A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60. Journal of Clinical Investigation 2022, Jul 1;132(13):e149906. PMID: 35653190.
- Inigo JR, Kumar R, and Chandra D. Targeting the mitochondrial unfolded protein response in cancer: opportunities and challenges. Trends in Cancer 2021, December, 7(12) 1050-1053. PMID: 34580036.
- O'Malley J, Kumar R, Inigo J, Yadava N, Chandra D. Mitochondrial Stress Response and Cancer. Trends in Cancer 2020, May 22:S2405-8033(20)30139-4. PMID: 32451306.
- 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 Research 2019, Apr 1;79(7):1353-1368. PMID: 30765600.
- 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 Letters 2017, Jul 1;397:52-60. PMID: 28342983.
- 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 & Disease 2015, Nov 5;6:e1969. PMID: 26539916.
- 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. PMID: 24086362.
- 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. Journal of Biological Chemistry 2013, Jan 4;288(1):368-81. PMID: 23152504.
- 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. Journal of Biological Chemistry 2011, Aug 19;286(33):28749-60. PMID: 21712378.
- 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. Journal of Biological Chemistry 2007, Oct 26;282(43):31289-301. 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. Molecular and Cellular Biology 2004, Aug;24(15):6592-607. PMID: 15254227.