Amitava Sengupta, MSc., Ph.D.

Senior Principal Scientist & Professor (AcSIR) Stem Cell & Leukemia lab, Head:
Cancer Biology & Inflammatory Disorder
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Research Focus

Molecular medicine of leukemia Acute myeloid leukemia (AML) pathogenesis; Innate immune sensing pathways & sterile inflammation in AML hematopoiesis; Epigenetic dependencies of immunomodulation

Research Interest

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 we are testing the hypothesis that epigenetic derangements within hematopoietic compartment contributes to AML pathogenesis. We are interested in investigating the cell-autonomous regulation of hematopoietic stem/progenitor cell transformation in AML, and leveraging unique epigenetic and transcriptional dependencies for immunomodulation. 

Additionally, age-related chronic inflammation emerges to be a driver in tumorigenesis, and growing single-cell multimodal studies have suggested that AML bone marrow ‘inflammation score’ correlates with leukemia evolution and therapy response. However molecular regulation of tumor cell-intrinsic sterile inflammatory cues driving clonal fitness and evolution in AML development in vivo is poorly understood. Employing relevant cellular and cutting edge physiological models of AML that includes analysis of primary diagnosis & relapsed AML patient derived hematopoietic stem/progenitor cells, CRISPR/Cas9 editing, syngenic models, transplantation assays, tumor vaccination studies into immunocompetent mice, cell line/AML patient derived xenografts into immunodeficient mice models, and epigenomic analyses we are dissecting molecular, cellular and physiological regulation of sterile inflammation and innate immune sensing pathways in the context of pre/leukemic hematopoiesis and evolution of AML immune microenvironment ecosystem. Ongoing/future research will harness the strength of single-cell multimodal analysis and computational biology for deeper understanding of sterile inflammation in leukemia. 

Overall we aim to: 

i) Investigate epigenetic mechanisms of hematopoietic stem/progenitor cell transformation in AML pathogenesis 
ii) Determine interplay between innate immune sensing & sterile inflammation in leukemic hematopoiesis 
iii) Examine and leverage epigenetic dependencies for immunomodulation 
iv) Study cellular plasticity & immune-inflammatory contexture within tumor microenvironment 

We have been privileged in establishing intra/inter-institutional, national and several exciting international collaborations with basic as well as physician scientists and computational biologists in addressing some of these challenging questions.

Our research is being funded by CSIR (MMP/HCP/OLP/P07/P50), Lady Tata Memorial Trust-Institutional Research Project Grant, DBT, SERB-DST, ICMR and Indo French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA).

Credentials

  • 2022   Sr. Principal Scientist, Stem Cell & Leukemia lab, CSIR-IICB & Professor, AcSIR 
  • 2019   Visiting Scientist, Princess Margaret Cancer Centre, University of Toronto, Canada 
  • 2018   Principal Scientist, Stem Cell & Leukemia lab, CSIR-IICB & Associate Professor, AcSIR
  • 2014   Senior Scientist, Stem Cell & Leukemia lab, CSIR-IICB & Assistant Professor, AcSIR
  • 2008-12  LTMT International Postdoctoral Fellow, Cincinnati Children’s Hospital Medical Center, USA 
  • 2008   PhD, Biotechnology, Jadavpur University & Saha Institute of Nuclear Physics, Kolkata
  • 2002   Post-MSc, Interdisciplinary Biophysical Sciences, Saha Institute of Nuclear Physics, Kolkata 
  • 2001   MSc, Biochemistry, University of Calcutta, Ballygunge Science College, Kolkata
  • 1999   BSc, Chemistry (Hons), University of Calcutta, Ramakrishna Mission Vivekananda Centenary College, Rahara

Honours & Awards

  • 2023 S Ramachandran National Bioscience Award for Career Development, Dept. of Biotechnology
  • 2023 American Society of Hematology (ASH) Abstract Achievement Award, San Diego, CA, USA (lab)
  • 2022 Bengal Society of Hematology, Prof. Sandhya Ghose Memorial Oration 
  • 2021 ICMR-National Institute of Immunohaematology (NIIH) Diamond Jubilee Oration Award 
  • 2021 Scholarship, Keystone Symposia: Hematopoiesis, USA (Invited Talk) 
  • 2021 Prof. Saroj Chandrasekhar Memorial Primary Award, Sastra University, (lab)
  • 2021 Scholarship, Keystone eSymposia: Epigenetics, Chromatin, Development & Disease 
  • 2019 ICMR-DHR International Fellowship for Senior Indian Biomedical Scientists, Govt. of India 
  • 2019 Keystone Symposia Global Health Travel Award, Croucher Foundation & Univ. Hong Kong 
  • 2018 Travel Award, International Society of Experimental Hematology (ISEH), CA, USA (lab) 
  • 2018 Cold Spring Harbor Asia (CSHA) Travel Award, (CSHA), Suzhou, China (lab) 
  • 2018 DBT-CTEP Travel Award, International Society for Stem Cell Research (ISSCR), Australia (lab) 
  • 2017 American Society of Hematology (ASH) Abstract Achievement Award, Atlanta, GA, USA (lab) 
  • 2011 Ramalingaswami Fellowship, Department of Biotechnology, Govt. of India
  • 2010 The Institute of Cancer Res, UK/Lady Tata Memorial Trust International 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 (ASH), CA, USA 
  • 2008 The Institute of Cancer Res, UK/Lady Tata Memorial Trust International 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

SELECTED PUBLICATIONS

  • Boila LD, Ghosh S, Bandyopadhyay SK, Jin L, Murison A, Zeng AGX, Shaikh W, Bhowmik S, Muddineni SSN, Biswas M, Sinha S, Chatterjee SS, Mbong N, Gan OI, Bose A, Chakraborty S, Arruda A, Kennedy JA, Mitchell A, Lechman ER, Banerjee D, Milyavsky M, Minden MD, Dick JE, Sengupta A. KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition. Leukemia 2023: 37, 751-764.
  • Boila LD, Sengupta A. Unifying targeted therapy for leukemia in the era of PARP inhibition. Experimental Hematology 2023: May 24:S0301-472X(23)00228-X
  • Chakraborty S, Sinha S, Sengupta A. Emerging trends in chromatin remodeler plasticity in mesenchymal stromal cell function. FASEB J 2021: 35, e21234
  • Boila LD, Sengupta A. Evolving insights on histone methylome regulation in human acute myeloid leukemia pathogenesis and targeted therapy. Experimental Hematology 2020: 92, 19-31.
  • Sinha S, Biswas M, Chatterjee SS, Kumar S, Sengupta A. Pbrm1 steers mesenchymal stromal cell osteolineage differentiation by integrating PBAF-dependent chromatin remodeling and BMP/TGF-β signaling. Cell Reports 2020: 31, 107570.
  • Sinha S, Chakraborty S, Sengupta A. Establishment of a Long-Term Co-culture Assay for Mesenchymal Stromal Cells and Hematopoietic Stem/Progenitors. STAR Protocols, 2020: 1, 100161.
  • Biswas M, Chatterjee SS, Boila LD, Chakraborty S, Banerjee D, Sengupta A. MBD3/NuRD loss participates with KDM6A program to promote DOCK5/8 expression and Rac GTPase activation in human acute myeloid leukemia. FASEB J 2019: 33, 5268-5286.
  • Saha S, Murmu KC, Biswas M, Chakraborty S, Basu J, Kolapalli SP, Chauhan S, Sengupta A, Prasad P. Transcriptomic analysis identifies RNA binding proteins as putative regulators of myelopoiesis and leukemia. Front Oncology 2019: 9, 692.
  • Chatterjee SS, Biswas M, Boila LD, Banerjee D, Sengupta A. SMARCB1 deficiency integrates epigenetic signals to oncogenic gene expression program maintenance in human acute myeloid leukemia. Mol Cancer Research 2018: 16, 791-804. AACR Featured Article
  • Sinha S, Chatterjee SS, Biswas M, Nag A, Banerjee D, De R, Sengupta A. SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors. Experimental Hematology 2018: 62, 39-44. ISEH Cover Page Article
  • 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. ACS Chemical Biology 2018: 13, 2003-2009.
  • Boila LD, Chatterjee SS, Banerjee D, Sengupta A. KDM6 and KDM4 demethylases emerge as molecular therapeutic targets in human acute myeloid leukemia. Experimental Hematology 2018: 58, 44-51.
  • 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. (1Co-first author) Cell Reports 2014: 9, 2084-2097.
  • 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. Nature Communications 2013: 4, 1660 doi: 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. Blood 2012: 119, 494-502.
  • 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. Blood 2012: 120, 800-811.
  • 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. Blood 2012: 119, 5144-5154.
  • 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. Proc Natl Acad Sci USA 2011: 108, 9957-9962.
  • Sengupta A, Cancelas JA. A conundrum in mammalian hematopoietic stem cell polarity. Cell Cycle 2011: 10, 4191-4192.
  • Sengupta A, Arnett JA, Dunn S, Williams DA, Cancelas JA. Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. Blood 2010: 116, 81-84.
  • Ryan MA, Nattamai KJ, Xing E, Schleimer D, Daria D, Sengupta A, Köhler 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. Nature Medicine 2010: 16, 1141-1146.
  • Sengupta A, Cancelas JA. Cancer Stem Cells: A stride towards cancer cure? J Cell Physiol 2010: 225, 7-14. Cover Page Article
  • Chakrabarty M, Sengupta A, Bhattacharya D, Banerjee S, Chakrabarti A. DNA binding domain of RFX5: Interaction with X-box DNA and RFXANK. Biochim et Biophys Acta 2010: 1804, 2016-2024.
  • Sengupta A, Banerjee S. Pleiotropic p27Kip1, BCR-ABL and Leukemic Stem Cell: The Trio in Concert. Leukemia 2007: 21, 2559-2561.
  • 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. Leukemia 2007: 21, 949-955.
  • 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. J Gene Med 2006: 8, 1251-1261. 

 

BOOK CHAPTERS

 Sinha S, Boila LD, Chatterjee SS, Sengupta A. miRNA and Cancer: A deadly liaison? Cancer and Noncoding RNAs, Elsevier Academic Press 2017: 27-46. 

Lead Organiser

International eSymposium on frontiers in Blood, cancer & development (fBcd21): systems to medicine, March 1-2, 2021

International Symposium on Frontiers in Development & Molecular Medicine (FDMM2019): models to insights, March 1-3, 2019 hosted by CSIR-IICB, Biswa Bangla Convention Center, Kolkata 

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