Aloke K Sarkar, Ph.D.
Department of Experimental Therapeutics, Division of Cancer Medicine
About Dr. Sarkar
Autophagy is an evolutionally conserved cellular degradation process involving elimination of defective or superfluous organelles and to target them to autophagosomes which eventually regulate both cell survival and cell death. Selective exclusion of damaged mitochondria by autophagy (mitophagy), in combination with mitochondrial biogenesis, regulates the changes in steady-state mitochondrial mass that are required to meet metabolic demand. I am particularly motivated to study mitochondria specific proteins that control the elimination of damaged and non-functional mitochondria in Leukemia. Recently we have identified a novel role for a DNA damage response pathway gene in regulating mitophagy in multiple cell types including B cell leukemia. Alternatively another area of my research interest is to identify new/novel cancer genes using insertional mutagenesis in genetically predisposed murine leukemia models. Using MoMuLV as many as 86 proviral integration sites were cloned that resulted in >35% acceleration in tumor induction when newborn transgenic mice are inoculated with the virus. I have identified several novel and yet undisclosed role of known genes in driving multiple human solid and liquid tumors including T and B cell leukemias. I am focused on identifying molecular targets of these genes in order to explore potential regulators that would help us designing strategy in future clinical trials.
Present Title & Affiliation
Assistant Professor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Education & Training
|1996||Jadavpur University, Calcutta, IND, PHD, Biochemistry & Cancer Biology|
|1987||University of Calcutta, Calcutta, IND, MS, Zoology & Genetics|
|2007-2011||Research Fellowship, Baylor College of Medicine, Houston, TX|
|2004-2007||Research Fellowship, University of Texas Medical Branch, Galveston, TX|
|2000-2004||Research Fellowship, University of Toronto, Toronto|
Experience & Service
Instructor, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2011 - 2020
Honors & Awards
|2004||SCCCB Postdoctoral Fellowship, University of Texas Medical Branch Galveston|
|2001||MRC Postdoctoral Fellowship, University of Toronto|
- Sarkar A, Stellrecht CM, Vangapandu HV, Ayres M, Kaipparettu BA, Park JH, Balakrishnan K, Burks JK, Pandita TK, Hittelman WN, Neelapu SS, Gandhi V. Ataxia telangiectasia mutated interacts with Parkin and induces mitophagy independent of kinase activity. Evidence from mantle cell lymphoma. Haematologica 2020 Feb 6. pii: haematol.2019.234385. doi: 10.3324/haematol.2019.234385(2):495-512, 2021. e-Pub 2021. PMID: 32029507.
- Sarkar A, Gandhi V. Activation of ATM kinase by ROS generated during ionophore- induced mitophagy in human T and B cell malignancies. Mol Cell Biochem Mol Cell Biochem 476, 2887 (2021). https://doi.org/10.1007/s11010-021-04183-5(1):2887-2887, 2021. e-Pub 2020. PMID: 32996079.
- Yi X, Sarkar A, Kismali G, Aslan B, Ayres M, Iles LR, Keating MJ, Wierda WG, Long JP, Bertilaccio MTS, Gandhi V. AMG-176, an Mcl-1 antagonist, shows preclinical efficacy in chronic lymphocytic leukemia. Clin Cancer Res 2020 Jan 14. pii: clincanres.1397.2019. doi: 10.1158/1078-0432.CCR-19-1397(14):3856-3867, 2020. e-Pub 2020. PMID: 31937611.
- Patel VM, Balakrishnan K, Douglas M, Tibbitts T, Xu EY, Kutok JL, Ayers M, Sarkar A, Guerrieri R, Wierda WG, O'Brien S, Jain N, Stern HM, Gandhi V. Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199). Leukemia 31(9):1872-1881, 2017. e-Pub 2016. PMID: 28017967.
- Sarkar A, Balakrishnan K, Chen J, Patel V, Neelapu SS, McMurray JS, Gandhi V. Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma. Oncotarget 7(3):3461-76, 2016. e-Pub 2015. PMID: 26658105.
- Sarkar A, Zhang M, Liu SH, Sarkar S, Brunicardi FC, Berger DH, Belaguli NS. Serum response factor expression is enriched in pancreatic β cells and regulates insulin gene expression. FASEB J 25(8):2592-603, 2011. e-Pub 2011. PMID: 21525490.
- Cui JW, Li YJ, Sarkar A, Brown J, Tan YH, Premyslova M, Michaud C, Iscove N, Wang GJ, Ben-David Y. Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation. Blood 110(Oct 1;110(7):2631-40. Epub 2007 Jun 22):2631-40, 2007. e-Pub 2007. PMID: 17586726.
- Lee CR, Cervi D, Truong AH, Li YJ, Sarkar A, Ben-David Y. Friend virus-induced erythroleukemias: a unique and well-defined mouse model for the development of leukemia. Anticancer Res 23(3A):2159-66, 2003. PMID: 12894591.
- Saha BK, Sarkar A, Basak R, Chatterjee M. 1alpha, 25-Dihydroxyvitamin D3 suppresses the effect of streptozotocin-induced diabetes during chemical rat liver carcinogenesis. Cell Biol Int 25(3):227-37, 2001. PMID: 11352495.
- Sarkar A, Saha BK, Basak R, Mukhopadhyay I, Karmakar R, Chatterjee M. Anticlastogenic potential of 1alpha,25-dihydroxyvitamin D3 in murine lymphoma. Cancer Lett 150(1):1-13, 2000. PMID: 10755381.
- Bishayee A, Sarkar A, Chatterjee M. Further evidence for chemopreventive potential of beta-carotene against experimental carcinogenesis: diethylnitrosamine-initiated and phenobarbital-promoted hepatocarcinogenesis is prevented more effectively by beta-carotene than by retinoic acid. Nutr Cancer 37(1):89-98, 2000. PMID: 10965525.
- Sarkar A, Pradhan S, Mukhopadhyay I, Bose SK, Roy S, Chatterjee M. Inhibition of early DNA-damage and chromosomal aberrations by Trianthema portulacastruml. In carbon tetrachloride-induced mouse liver damage. Cell Biol Int 23(10):703-8, 1999. PMID: 10736194.
- Sarkar A, Basak R, Bishayee A, Basak J, Chatterjee M. Beta-carotene inhibits rat liver chromosomal aberrations and DNA chain break after a single injection of diethylnitrosamine. Br J Cancer 76(7):855-61, 1997. PMID: 9328143.
- Mukherjee B, Sarkar A, Chatterjee M. Biochemical basis of selenomethionine-mediated inhibition during 2-acetylaminofluorene-induced hepatocarcinogenesis in the rat. Eur J Cancer Prev 5(6):455-63, 1996. PMID: 9061276.
- Sarkar A, Bishayee A, Chatterjee M. Beta-carotene prevents lipid peroxidation and red blood cell membrane protein damage in experimental hepatocarcinogenesis. Cancer Biochem Biophys 15(2):111-25, 1995. PMID: 8590436.
- Bishayee A, Sarkar A, Chatterjee M. Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. J Ethnopharmacol 47(2):69-74, 1995. PMID: 7500638.
- Sarkar A, Mukherjee B, Chatterjee M. Inhibition of 3'-methyl-4-dimethylaminoazobenzene-induced hepatocarcinogenesis in rat by dietary beta-carotene: changes in hepatic anti-oxidant defense enzyme levels. Int J Cancer 61(6):799-805, 1995. PMID: 7790114.
- Sarkar A, Mukherjee B, Chatterjee M. Inhibitory effect of beta-carotene on chronic 2-acetylaminofluorene induced hepatocarcinogenesis in rat: reflection in hepatic drug metabolism. Carcinogenesis 15(5):1055-60, 1994. PMID: 8200068.
- Sarkar A, Mukherjee B, Rana M, Chatterjee M. Comparative patterns of hepatic drug metabolizing enzymes and their possible correlation with chromosomal aberrations in transplantable murine lymphoma: a time course study. Cancer Invest 12(5):477-83, 1994. PMID: 7922703.
- Tantawy SI, Sarkar A, Hubner S, Tan Z, Wierda WG, Eldeib A, Zhang S, Kornblau S, and Gandhi V. Mechanisms of MCL-1 protein stability induced by MCL-1 antagonists in CLL. Clin Cancer Res.
- Sarkar A, Pandita TK and Gandhi V. Hsp90-Tom70 interaction facilitates ATM localization to mitochondria and induces mitochondrial autophagy. Cancer Research. Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA, 2016.
- Sarkar A, Balakrishnan K and Gandhi V. MK2206 disrupts cytoplasmic AKT-p21 complex in mantle cell lymphoma: Evidence of p21 coupled cell cycle arrest. Cancer Research. Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA, 2015.
- Sarkar A, Balakrishnan K, Ayres M, Neelapu SS and Gandhi V. Essential role of ataxia telangiectasia in mitochondrial autophagy in mantle cell lymphoma. Cancer Research. Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA, 2014.
- Sarkar A, Chen J, Neelapu SS, Balakrishnan K and Gandhi V. L14R8, a Pac derivative, induces casapase-3 mediated apoptosis in mantle cell lymphoma. Cancer Research. Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. DOI: 10.1158/1538-7445. AM2013-3347 Published April 2013, 2013. e-Pub 2013.
- Belaguli NS, Sarkar A, Zhang M, Rigi M, Berger DH. Regulation of Pdx-l and Insulin Gene Expression by Serum Response Factor. American Diabetes Association Abstract # 1632-P, 2008.
Grant & Contract Support
|Title:||Deciphering the role of Ataxia Telangiectasia Mutated in mitochondrial autophagy in cancer|
|Funding Source:||MDACC IRG|