Hemanta K. Majumder , Ph.D, FNA, FASc., FNASc., FAScT, FTWAS, NASI- Senior Scientist Platinum Jubilee Fellow, Sir J.C. Bose National Fellow (DST )

Senior Scientist NASI
Infectious Diseases and Immunology
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Research Focus

Kinetoplastid protozoa, Leishmania donovani, Topoisomerase

Research Interest

For more than three decades Dr. H.K. Majumder has been working on the molecular biology of Leishmania donovani, the causative agent of visceral leishmaniasis. He has made significant contribution in biochemistry of DNA topoisomerases of Leishmania with reference to development of therapeutics. His area of research includes (i) basic DNA enzymology of topoisomerases (ii) development of antileishmanial compounds targeted to DNA topoisomerases (iii) cell death of the parasites induced by DNA topoisomerases inhibitors and, (iv) development of kinetoplast DNA based PCR diagnostics. 

His group has characterized type IB, type II, and other topoisomerases like topo IIIA and topo IIIB in this parasite. The breakthrough contribution of the group is the discovery and characterization of heterodimeric type IB topoisomerase in Leishmania completely different from higher eukaryotes. His group has established that large subunit (LdTOPIL) functions as a molecular steer and a small subunit (LdTOPIS) harbors the catalytic activity. Fusion of these two subunits leads to the active enzyme (LdTOPIB) in Leishmania donovani.

Over the last decade, his laboratory has been involved to search for DNA topoisomerase targeted novel antileishmanial agents.  He has established the efficacies of several compounds, both natural and synthetic, to kill parasites. Some of the compounds have been shown to give promising results in experimental mice model of leishmaniasis. Dr. Majumder’s group has established the molecular algorithm of apoptosis-like cell death in Leishmania triggered by Camptothecin (a well-known topoisomerase targeted anticancer drug) for the first time. He is also trying to understand the ultrastructural alterations, particularly in nucleus and mitochondria, in Leishmania due to topoisomerase malfunctioning.

Credentials

  1. Elected Fellow of the World Academy of Sciences (FTWAS)
  2. Elected Fellow of the Indian National Science Academy (FNA)
  3. Elected Fellow of the Indian Academy of Sciences (FASc)
  4. Fellow of the National Academy of Sciences (FNASc), India
  5. Fellow of the Academy of Science & Technology (FAScT), W. B.
  6. Indian Science Congress Association (ISCA) (life Member)
  7. Guha Research Conference (GRC) Elected Member
  8. Society of Biological Chemists (SBC-1)Life Member/Ex Vice President
  9. Association for DNA finger printing & Technology (Life Member)
  10. Indian Society for Cell Biology (ISCB)     (Life Member)
  11. Administrative Staff College of India (ASCI) (Life Member)
  12. Member of the Bio Safety Committee of Calcutta University
  13. Chairman of the Institutional Ethics Committee, Institute of Post Graduate Medical Education & Research (IPGMER), Kolkata
  14. Member of the Board of Studies in Biotechnology, St. Xaviers College, Kolkata
  15. Member of the Board of Studies in Microbiology, Lady Brabourne college, Kolkata
  16. Member of the Selection Committee for Senior Research Fellow (SRF) and Research Associate (RA) in Section Life Science- 12 of HRD of CSIR, New Delhi
  17. Member of the Infectious Disease Biology Task Force (IDBTF) of DBT, Govt. of India (2012-2015).
  18. Member of the Research Advisory Committee of the Central Sericulture Research & Training Institute, Berhampur, Murshidabad, West Bengal.
  19. Convener, Local Chapter of Indian National Science Academy (2012-present)
  20. Member, Board of Studies, Assam University, Silchar (2012 - till date)
  21. Chancellor’s Nominee for the Court of Kalyani University (2017 - till date)
  22. Member of the Senate of IISER Kolkata (2010 -2013)
  23. Chairman, Local Chapter of National Academy of Sciences, India (2009-present)
  24. Member of the “Technical Screening Committee of Small Business Innovation Research Initiative (SBIRI), Department of Biotechnology (DBT), Govt. of India. (2008-2010).
  25. Chairman, State Level Climatic Change Committee, Govt. of West Bengal (2006-2011).
  26. Member of the Research Advisory Council Vector Control Research Center, Pondicherry (2005 – 2009)
  27. Member of the Question Bank Committee of KVPY 2005
  28. Chairman, Expert Committee for State Innovation Award, Govt. of West Bengal (2004-2011).
  29. Working Chairman, West Bengal State Council of Science and Technology ( WBSCST) (2004-2011)
  30. Member of the Selection Committee for Scholarships to the High School and Under Graduate students under Kishore Vaigyanik Protsahan Yojana (KVPY) sponsored by DST, Govt. of India for year 2000-2003 

Honours & Awards

  • C. V. Raman Birth Centenary Award by Indian Science Congress Association (2018) (Award to be given in 106th Indian Science Congress, January 3 – 7, 2019)
  • Sir Ronald Ross Memorial 57th Foundation Day Oration Lecture Award of Institute of Post Graduate Medical Education and Research (IPGMER), Kolkata (2013)
  • Raja Ramanna Fellowship by Department of Atomic Energy, Govt. of India (2012-2016)
  • Nitya Anand Endowment Lecture Award for outstanding work in Biomedical Research including New Drug Development by Indian National Science Academy (INSA) (2012)
  • Sir J. C. Bose National Fellowship by Department of Science and Technology, Govt. of India (2010-2016)
  • Desh Ratna Dr. Rajendra Prasad Memorial Lecture Award by Rajendra Memorial Research Institute, ICMR, Patna (2008)
  • Prof. Jnan Chandra Ghosh Memorial Award by Science Association of Bengal for excellent contribution in the field of science & technology, research promotion and development in India and abroad (2007)
  • Prof. B. K. Bachhawat Memorial Lecture Award by National Academy of Sciences, India (2007)
  • Dr. P. C. Sengupta Memorial Oration Gold Medal by Calcutta School of Tropical Medicine for outstanding contribution in Kala-azar research (2004)

Grants & Supports

NASI-Senior Scientist Platinum Jubilee Fellowship-Research Grant

Patents & Publications

  1. Chowdhury SR, Godinho JLP, Vinayagam J, Zuma AA, Silva STM, Jaisankar P, Rodrigues JCF, De Souza W, Majumder HK. Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites. Sci Rep, 8(1), 1, 11940 (2018) Nature Publishing Group
  2. Muthu Ramalingam B, Dhatchana Moorthy N, Chowdhury SR, Mageshwaran T, Vellaichamy E, Saha S, Ganesan K, Rajesh BN, Iqbal S, Majumder HK, Gunasekaran K, Siva R, Mohanakrishnan AK. Synthesis and Biological Evaluation of Calothrixins B and their Deoxygenated Analogues. J Med Chem, 61, 3, 1285-1315 (2018) ACS Publication
  3. Chowdhury SR, Kumar A, Godinho JLP, De Macedo Silva ST, Zuma AA, Saha S, Kumari N, Rodrigues JCF, Sundar S, Dujardin JC, Roy S, De Souza W, Mukhopadhyay S, Majumder HK. Voacamine alters Leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase IB; Biochem Pharmacol, 138, NA, 19-30 (2017) ELSEVIER
  4. Saha S, Acharya C, Pal U, Chowdhury SR, Sarkar K, Maiti NC, Jaisankar P, Majumder HK. A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase Antimicrob Agents Chemother, 60, 10, 6281-6293 (2016) American Society for Microbiology
  5. Jain CK, Roychoudhury S, Majumder HK. Selective killing of G2 decatenation checkpoint defective colon cancer cells by catalytic topoisomerase II inhibitor. Biochim Biophys Acta, 1853, 5, 1195-1204 (2015) BBA
  6. Chowdhury S, Mukhopadhyay R, Saha S, Mishra A, Sengupta S, Roy S, Majumder HK Flavone-resistant Leishmania donovani overexpresses LdMRP2 transporter in the parasite and activates host MRP2 on macrophages to circumvent the flavone-mediated cell death. J Biol Chem, 289, 23, 16129-16147 (2014) American Society for Biochemistry and Molecular Biology, Inc.
  7. Das BB, Huang SY, Murai J, Rehman I, Amé JC, Sengupta S, Das SK, Majumdar P, Zhang H, Biard D, Majumder HK, Schreiber V, Pommier Y. PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage. Nucleic Acids Res, 42, 7, 4435-4449 (2014) Oxford Academic
  8. Saha S, Mukherjee T, Chowdhury S, Mishra A, Chowdhury SR, Jaisankar P, Mukhopadhyay S, Majumder HK The lignan glycosides lyoniside and saracoside poison the unusual type IB topoisomerase of Leishmania donovani and kill the parasite both in vitro and in vivo. Biochem Pharmacol, 86, 12, 1673-1687 (2013) ELSEVIER
  9. Chowdhury S, Mukherjee T, Mukhopadhyay R, Mukherjee B, Sengupta S, Chattopadhyay S, Jaisankar P, Roy S, Majumder HK. The lignan niranthin poisons Leishmania donovani topoisomerase IB and favours a Th1 immune response in mice. EMBO Mol Med, 4, 10, 1126-1143 (2012) European Molecular Biology Organization (EMBO)
  10. Sengupta S, Ganguly A, Roy A, Bosedasgupta S, D'Annessa I, Desideri A, Majumder HK. ATP independent type IB topoisomerase of Leishmania donovani is stimulated by ATP: an insight into the functional mechanism. Nucleic Acids Res, 39, 83295-3309 (2011) Oxford Academic
  11. Banerjee B, Roy A, Sen N, Majumder HK. A tyrosyl DNA phosphodiesterase 1 from kinetoplastid parasite Leishmania donovani (LdTdp1) capable of removing topo I-DNA covalent complexes. Mol Microbiol,78, 1, 119-137 (2010) Wiley-Blackwell
  12. Roy A, BoseDasgupta S, Ganguly A, Jaisankar P, Majumder HK. Topoisomerase I gene mutations at F270 in the large subunit and N184 in the small subunit contribute to the resistance mechanism of the unicellular parasite Leishmania donovani towards 3,3'-diindolylmethane. Antimicrob Agents Chemother, 53, 6, 2589-2598 (2009) American Society for Microbiology
  13. BoseDasgupta S, Das BB, Sengupta S, Ganguly A, Roy A, Dey S, Tripathi G, Dinda B, Majumder HK. The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA 'degradesome'. Cell Death Differ,15,10, 1629-1640 (2008) Nature Publishing Group
  14. Ganguly A, Das B, Roy A, Sen N, Dasgupta SB, Mukhopadhayay S, Majumder HK. Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death. Cancer Res, 67, 24, 11848-11858 (2007) American Association for Cancer Research (AACR)
  15. Das BB, Bose Dasgupta S, Ganguly A, Mazumder S, Roy A, Majumder HK. Leishmania donovani bisubunit topoisomerase I gene fusion leads to an active enzyme with conserved type IB enzyme function. FEBS J, 274, 1, 150-163 (2007) Federation of European Biochemical Societies (FEBS)
  16. Sen N, Banerjee B, Das BB, Ganguly A, Sen T, Pramanik S, Mukhopadhyay S, Majumder HK. Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex. Cell Death Differ, 14, 2, 358-67 (2007) Nature Publishing Group
  17. Ganguly A, Das BB, Sen N, Roy A, Dasgupta SB, Majumder HK. 'LeishMan' topoisomerase I: an ideal chimera for unraveling the role of the small subunit of unusual bi-subunit topoisomerase I from Leishmania donovani. Nucleic Acids Res, 34, 21, 6286-6297 (2006) Oxford Academic
  18. Das BB, Sen N, Roy A, Dasgupta SB, Ganguly A, Mohanta BC, Dinda B, Majumder HK. Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I. Nucleic Acids Res, 34, 4, 1121-1132 (200) Oxford Academic
  19. Sengupta T, Mukherjee M, Das R, Das A, Majumder HK. Characterization of the DNA-binding domain and identification of the active site residue in the 'Gyr A' half of Leishmania donovani topoisomerase II. Nucleic Acids Res, 33, 8, 2364-2373 (2005) Oxford Academic
  20. Das BB, Sen N, Dasgupta SB, Ganguly A, Majumder HK. N-terminal region of the large subunit of Leishmania donovani bisubunit topoisomerase I is involved in DNA relaxation and interaction with the smaller subunit. J Biol Chem, 280, 16, 16335-16344 (2005) American Society for Biochemistry and Molecular Biology, Inc.
  21. Sen N, Das BB, Ganguly A, Mukherjee T, Bandyopadhyay S, Majumder HK. Camptothecin-induced imbalance in intracellular cation homeostasis regulates programmed cell death in unicellular hemoflagellate Leishmania donovani. J Biol Chem, 279, 50, 52366-52375 (2004) American Society for Biochemistry and Molecular Biology, Inc.
  22. Das BB, Sen N, Ganguly A, Majumder HK. Reconstitution and functional characterization of the unusual bi-subunit type I DNA topoisomerase from Leishmania donovani. FEBS Lett, 565, 1-3, 81-88 (2004) Federation of European Biochemical Societies (FEBS)
  23. Sen N, Das BB, Ganguly A, Mukherjee T, Tripathi G, Bandyopadhyay S, Rakshit S, Sen T, Majumder HK. Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani. Cell Death Differ, 11, 8, 924-936 (2004) Nature Publishing Group
  24. Sengupta T, Mukherjee M, Mandal C, Das A, Majumder HK. Functional dissection of the C-terminal domain of type II DNA topoisomerase from the kinetoplastid hemoflagellate Leishmania donovani. Nucleic Acids Res, 31, 18, 5305-5316 (2003) Oxford Academic
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