Amitava Sengupta , Ph.D.
Cancer Biology & Inflammatory Disorder
Epigenetic regulation in hematopoiesis & acute myeloid leukemia (AML) pathophysiology
Stem cells possess two fundamental properties; self-renewal and differentiation. Bone marrow-resident adult hematopoietic stem cells (HSC) respond to physiological stimuli and regenerate hematopoiesis. Dysregulated self-renewal and arrest in differentiation of HSC and progenitors induce leukemic transformation.
Physiological aging is associated with the onset of chronic and lifestyle diseases including cancer. Hematopoietic aging is characterized by clonal expansion of myeloid-biased hematopoietic stem cells/ progenitors and by increased risk of development of myeloid leukemia. Although the majority of patients with acute myeloid leukemia (AML; one form of blood cancer) initially respond to chemotherapy, many of them subsequently relapse, and the mechanistic basis for AML persistence following chemotherapy remains poorly understood.
In our laboratory at IICB we have been trying to test the hypothesis that epigenetic dysregulation within hematopoietic compartment is involved in hematopoietic aging and causes AML pathogenesis. We are particularly interested at understanding the cell-autonomous and non-cell-autonomous molecular determinants that regulate HSC self-renewal, differentiation and interaction with hematopoietic microenvironment or niche.
Precisely we are addressing i) Cell-autonomous mechanisms of hematopoietic stem cell transformation, ii) Epigenetic regulation of leukemia stem cell heterogeneity and iii) Microenvironment regulation in hematopoiesis.
In addition, from a translational perspective HSCs draw attention because of their potential use in stem cell and gene therapy. Presently we are engaged in CSIR Mission Mode Program on Sickle Cell Anemia towards targeted gene editing in order to restore sickle cell phenotype with an aim to foster pre/clinical translation for autologous gene/cell therapy.
Our overreaching aim is identification of altered and unique epigenetic fingerprints in human hematopoietic aging, myeloid leukemia pathobiology, and characterization of synthetically lethal epigenetic vulnerabilities in AML.
- 2014 Senior Scientist, Stem Cell & Leukemia Lab, CSIR-IICB, Kolkata & Assistant Professor, AcSIR
- 2013 Ramalingaswami Fellowship, Department of Biotechnology, Govt. of Indi
- 2007-12 The Institute of Cancer Research, UK/Lady Tata Memorial Trust International Postdoctoral Fellow, Stem Cell Program, Division of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, OH, USA
- 2008 Ph.D., Biotechnology, Jadavpur University
- 2002 Post M.Sc., Biophysical Sciences, Saha Institute of Nuclear Physics, Kolkata
- 2001 M.Sc., Department of Biochemistry, University of Calcutta
- 1999 B.Sc., Chemistry, Rahara Vivekananda Centenary College, University of Calcutta
Honours & Awards
- 2017 American Society of Hematology (ASH) Abstract Achievement Award, Atlanta, GA, USA
- 2012 Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India
- 2011 The Institute of Cancer Res., UK/Lady Tata Memorial Trust Int. Postdoc Fellowship, USA
- 2009 Travel Award, American Society of Hematology (ASH), LA, USA
- 2008 Travel Award, International Society of Experimental Hematology (ISEH), MA, USA
- 2008 Travel Award, American Society of Hematology, CA, USA
- 2008 The Institute of Cancer Res., UK/Lady Tata Memorial Trust Int. Postdoc Fellowship, USA
- 2008 Graduate Aptitude Test in Engineering Fellowship, IIT, Kanpur, India (declined)
- 2001 Shanti Bhakta Memorial Award, Dept. of Biochemistry, Univ. of Calcutta, India
- 1996 Certificate of Merit, West Bengal Teachers’ Association, West Bengal, India
- 1994 Scholarship, West Bengal Board of Secondary Education, West Bengal, India
Patents & Publications
- Chatterjee SS1, Biswas M1, Boila LD, Banerjee D, Sengupta A* ; SMARCB1 deficiency integrates epigenetic signals to oncogenic gene expression program maintenance in human acute myeloid leukemia. 2018 , Molecular Cancer Research (AACR, Highlighted Article) , 16 , 791-804 , 29483235 , 10.1158/1541-7786.MCR-17-0493
- Sinha S, Chatterjee SS2, Biswas M2, Nag A, Banerjee D, De R, Sengupta A* ; SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors. 2018 , Experimental Hematology (ISEH, Cover Page) , 62 , 39-44 , 29596882 , 10.1016/j.exphem.2018.03.005
- Boila LD, Chatterjee SS, Banerjee D, Sengupta A* ; KDM6 and KDM4 demethylases emerge as molecular therapeutic targets in human acute myeloid leukemia. 2018 , Experimental Hematology (ISEH) , 58 , 44-51 , 29111428 , 10.1016/j.exphem.2017.10.002
- Ghosh B, Boila LD, Choudhury S, Mondal P, Bhattacharjee S, Pal SK, Sengupta A, Roy S ; A potent conformation-constrained synthetic peptide mimic of a homeodomain selectively regulates target genes in cells. 2018 , ACS Chemical Biology , 13 , 2003-2009 , 29966078 , 10.1021/acschembio.8b00488
- Biswas M1, Chatterjee SS1, Boila LD, Banerjee D, Sengupta A* ; NuRD loss amplifies histone demethylase-dependent oncogenic gene expression and sensitizes human AML cells to Rac GEF inhibition. na , FASEB J (in revision) , na , na , na , na
- Chang KH1, Sengupta A1, Nayak R, Duran A, Lee SJ, Pratt R, Wellendorf AM, Hill SE, Watkins M, Gonzalez-Nieto D, Aronow BJ, Starczynowski DT, Civitelli R, Diaz-Meco MT, Moscat J, Cancelas JA ; p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow, macrophage-osteoblast niche. 2014 , Cell Reports , 9 , 2084-2097 , 25533346 , 10.1016/j.celrep.2014.11.031
- Taniguchi Ishikawa E, Chang KH, Nayak R, Olsson HA, Ficker A, Dunn SK, Madhu MN, Sengupta A, Whitsett JA, Grimes HL, Cancelas JA ; Kruppel-like-factor 5 (Klf5) controls bone marrow lodging of hematopoetic stem cells and progenitors through Rab5-mediated active β1–integrin expression. 2013 , Nature Communications , 4 , 1660 , na , 10.1038/ncomms2645
- Sengupta A, Ficker A, Dunn S, Madhu M, Cancelas JA ; Bmi1 reprograms chronic myelogenous leukemia B-lymphoid progenitors to become B-ALL-initiating cells. 2012 , Blood , 119 , 494-502 , 22101899 , 10.1182/blood-2011-06-359232
- Gonzalez-Nieto D, Li L, Kohler A, Ghiaur G, Ishikawa E, Sengupta A, Madhu M, Arnett J, Santho R, Dunn S, Fishman I, Gutstein D, Civitelli R, Barrio LC, Gunzer M, Cancelas JA ; Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors. 2012 , Blood , 119 , 5144-5154 , 22498741 , 10.1182/blood-2011-07-368506
- Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu M, Ficker A, Dunn S, Arnett J, Santo R, Agirre X, Perentesis J, Deininger M, Bustelo X, Williams DA, Cancelas JA ; Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation and survival. 2012 , Blood , 120 , 800-811 , 22692505 , 10.1182/blood-2011-06-361709
- Sengupta A, Duran A, Ishikawa E, Florian M, Dunn S, Ficker A, Leitges M, Geiger H, Diaz-Meco MT, Moscat J, Cancelas JA ; aPKCζ and aPKCλ are dispensable in hematopoietic stem cell activity and blood formation. 2011 , Proc Natl Acad Sci USA , 108 , 9957-9962 , 21653884 , 10.1073/pnas.1103132108
- Sengupta A, Cancelas JA ; A conundrum in mammalian hematopoietic stem cell polarity. 2011 , Cell Cycle , 10 , 4191-4192 , 22157228 , 10.4161/cc.10.24.18361
- Sengupta A, Arnett JA, Dunn S, Williams DA, Cancelas JA ; Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. 2010 , Blood , 116 , 81-84 , 20407032 , 10.1182/blood-2009-10-247437
- Ryan MA, Nattamai KJ, Xing E, Schleimer D, Daria D, Sengupta A, Kohler A, Liu W, Gunzer M, Jansen M, Ratner N, Le Cras TD, Waterstrat A, Van Zant G, Cancelas JA, Zheng Y, Geiger H ; Pharmacological inhibition of EGFR signaling enhances G-CSF induced HSC mobilization. 2010 , Nature Medicine , 16 , 1141-1146 , 20871610 , 10.1038/nm.2217
- Sengupta A, Cancelas JA ; Cancer Stem Cells: A stride towards cancer cure? 2010 , J Cell Physiology (Highlighted Article) , 225 , 14-Jul , 20458736 , 10.1002/jcp.22213
- Chakrabarty M, Sengupta A, Bhattacharya D, Banerjee S, Chakrabarti A ; DNA binding domain of RFX5: Interaction with X-box DNA and RFXANK. 2010 , Biochim et Biophys Acta , 1804 , 2016-2024 , 20637319 , 10.1016/j.bbapap.2010.07.009
- Sengupta A, Banerjee D, Chandra S, Banerji SK, Ghosh R, Roy R, Banerjee S ; Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. 2007 , Leukemia , 21 , 949-955 , 17361218 , 10.1038/sj.leu.2404657
- Sengupta A, Banerjee S ; Pleiotropic p27Kip1, BCR-ABL and Leukemic Stem Cell: The Trio in Concert. 2007 , Leukemia , 21 , 2559-2561 , 17611557 , 10.1038/sj.leu.2404842
- Sengupta A, Banerjee D, Chandra S, Banerjee S ; Gene therapy for BCR-ABL+ human CML with dual phosphorylation resistant p27Kip1 and stable RNA interference using an EBV vector. 2006 , J Gene Medicine , 8 , 1251-1261 , 16952195 , 10.1002/jgm.959
Sinha S,1 Boila LD,1 Chatterjee SS,1 Sengupta A*. miRNA and Cancer: A deadly liaison? Cancer and Noncoding RNAs, Elsevier 2017: 27-46.