Cell death is one of the fundamental biological processes required to maintain normal development. A cell’s decision to live or die is tightly regulated by signals originating from various sources. Our interest is to elucidate the regulatory processes of cell death and the associated mechanisms.
Summary of Research:
The course of evolution has shaped different species for their survival during conditions of stress, natural development, differentiation and growth. These conditions represent the two faces of the same coin because continued growth or continuous stress would hamper survival. To circumvent these problems, all animal cells have evolved the capability to kill themselves by turning on gene-encoded cell suicide programs. These programs not only help the organisms to survive in conditions of excessive stress but also help prevent abnormal growth. The decision of whether a particular cell will live or die is tightly regulated by many different signals originating both from within the cell and from its environment. The implementation of this self-destruction program leads to a morphologically distinct form of cell death termed apoptosis and deregulation of apoptosis is associated with a variety of diseases including cancer, autoimmune diseases and neurodegenerative disorders. There are considerable variations in which apoptosis occur in different systems and under different conditions. Cell death also occurs via processes such as programmed necrosis and autophagy and it is the balance between survival and these death processes that determines the fate of a cell. The major focus of the laboratory is to elucidate the precise mechanisms of cell death and how this process is regulated by the diverse signalling pathways using unicellular (Leishmania parasite) and multicellular (cancer cells) model systems with or without genetic manipulations. The aim is to provide a deeper understanding of cell death events that can help in the development of improved therapeutics for diseases associated with anomalous cell death.
Ashish Kumar, Sagnik Giri, Durgesh Pitale, Sanchita Das, G.S. Neelaram, Vineet Singh and Shipra Sankla
• 2019: Shanti Swarup Bhatnagar Medal, INSA
• 2017: Sectional President, Biological Sciences, National Academy of Sciences.
• 2016: Elected, Vice-president of the Indian National Science Academy, Delhi
• 2016: Elected, Council Member of National Academy of Sciences, Allahabad.
• 2015: Sunday Standard Devi Award for excellence in the field of science
• 2015: Om Prakash Bhasin Award for excellence in Biotechnology Research
• 2014: Elected, Council Member, Indian National Science Academy
• 2014: Elected Fellow, The World Academy of Sciences (TWAS), Trieste. Italy
• 2014: 14th Pushpa Sriramachari Foundation Day Oration Award, ICMR.
• 2013: Prof. (Mrs). Archana Sharma Memorial Award, National Academy of Sciences
• 2013: Chandrakala Hora Memorial Medal, Indian National Science Academy.
• 2011: Elected, Fellow of West Bengal Academy of Science and Technology
• 2010: Ranbaxy Science Foundation Award for Basic Medical Research
• 2010: Darshan Ranganathan Memorial Lecture Award, Indian National Science Academy.
• 2009: J.C. Bose National Fellowship, Dept. of Science and Technology.
• 2008: Elected Fellow, Indian National Science Academy, Delhi
• 2004: Elected Fellow, Indian Academy of Sciences, Bangalore
• 2003: Department of Biotechnology ‘Special Award’
• 1999: Elected Fellow, The National Academy of Sciences, Allahabad, India
• 1992: Shakuntala Amirchand Award of Indian Council of Medical Research
- Pitale DM, Neelaram GS, Descoteaux A and Shaha, C*. Leishmania donovani induces autophagy in human blood-derived neutrophils. J. Immunol. 202:1163-1175 (2019).
- Das S and Shaha C* Cellular Defence of the Leishmania Parasite. Molecular Biology of the Kinetoplastid parasites. (Ed. H.K. Majumder. Caister Academic Press, UK) DOI: https://doi.org/10.21775 /9781910190715.04 pp 67-80. (2018)
- Kumar A, Giri S and Shaha C* Sestrin2 facilitates glutamine dependent transcription of PGC1-α and survival of liver cancer cells under glucose limitation. FEBS J. DOI: 10.1111/febs.14406 (2018)
- Kumar A and Shaha C* SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci Rep 8:615, DOI: 10.1038/s41598-017-19102-2. (2018)
- Kumar, A and Shaha, C*. RBX1 mediated ubiquitination of SESN2 promotes cell death upon prolonged mitochondrial damage in SH-SY5Y neuroblastoma cells. Molecular and Cellular Biochemistry DOI: 10.1007/s11010-017-3267-7 (2018).
- Chang KP, Kohli BK and collaborators (Shaha C, Saha G Roy S and Mukhopadhyay A)( Overview of Leishmaniasis with special emphasis on Kala Azar in South Asia. Neglected Tropical diseases. doi.org/10.1007/978-3-319-68493-2_1 (2017).
- Das, S., Giri, S, S. Sundar and Shaha, C*, Leishmania donovani Tryparedoxin Peroxidases: functional involvement during infection and drug treatment. Antimicrob. Agents. Chem. Antimicrob. Agents. Chem.doi:10.1128/AAC.00806-17, (2017).
- Saini, S, Bharti, K., Shaha, C., Mukhopadhay C. Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony resistant Leishmania donovani. Scientific Reports. 7: 10488 | DOI: 10.1038/s41598-017-10041-6 2 (2017)
- Pandey RK, Mehrotra S, Sharma S, Gudde RS, Sundar S, Shaha C*. Leishmania donovani-Induced Increase in Macrophage Bcl-2 Favors Parasite Survival. Front Immunol. 7:456. (2016).
- Singh AK, Pandey RK, Shaha C and Madhubala R. MicroRNA expression profiling of Leishmaniadonovani infected host cells uncovers the regulatory role of MIR-30A-30 in host autophagy. Autophagy. 12: 1817- 1831(2016).
- R. Mathur, R.P. Das, A. Ranjan, C. Shaha* Elevated ergosterol protects Leishmania parasites against antimony-generated stress FASEB J 29:4201-13 (2015).
- S. Das, A. Aich and C. Shaha*. The Complex World of Leishmania defense. Proceedings of the Indian National Science Academy, 81, 629-642, (2015).
- D. Ash, M. Subramanian, A. Surolia and C. Shaha*. Nitric oxide is the key mediator of death induced by fisetin in human acute monocytic leukemia cells. Am. J. Cancer Res.5 (2), 481-497 (2015).
- R. Mathur and C. Shaha*, Cell death in a kinetoplastid parasite, the Leishmania spp. In Leishmania: Genomics, Molecular Biology and Control. Ed: S. Adak. Horizon Scientific Press, UK. Pp 79-92 (2014).
- R.Tripathi, D. Ash and C. Shaha*, Beclin-1 p53 interaction is crucial for cell fate determination in embryonal carcinoma cells. J. Cell. Mol. Med. 18: 2275-2286 (2014).
- A. Aich and C. Shaha*, Novel role of calmodulin in regulating protein transport to mitochondria in a unicellular eukaryote. Mol. Cell Biol.33:22 4579-4593 (2013).
- S. Verma, A. Mehta and C. Shaha.* CYP5122A1, a novel cytochrome P450 is essential for survival of Leishmania donovani. Plos One 6:e25273 (2011).
- R. Tripathi, T. Samadder, S. Gupta, A. Surolia and C. Shaha*, Anti-cancer activity of a combination of cisplatin and fisetin in embryonal carcinoma cells and xenograft tumors. Mol. Cancer. Ther.10:255-268 (2011).
- R. Jain, A. Ghoshal, C. Mandal and C. Shaha C*. Leishmania cell surface prohibitin: role in host-parasite interaction. Cell. Microbiol. 12:432-452 (2010).
- M. Subramanian and C. Shaha* Oestrogen modulates human macrophage apoptosis via differential signaling through oestrogen receptor alpha and beta. J Cell Mol Med.13:2317-29 (2009).
- C.Shaha* Estrogens and Spermatogenesis. Adv. Exp. Med. Biol. 636:42-64 (2009).
- J. Iyer, A. Kaprakkaden, M. Chaudhary and C.Shaha*, Crucial role of cytosolic tryparedoxin peroxidase in Leishmania donovani survival, drug response and virulence. Mol. Microbiol. 68: 372-391 (2008).
- M. Subramanian and C. Shaha* Up-Regulation of Bcl-2 through ERK Phosphorylation Is Associated with Human Macrophage Survival in an Estrogen Microenvironment. J. Immunol. 179:2330-2338 (2007).
- A. Mehta and C. Shaha*. Mechanism of metalloid induced death in Leishmania spp.: role of iron, reactive oxygen species, Ca2+ and glutathione. Free Rad. Biol. Med. 15:1857-68 (2006).
- D. P. Mishra, Rajarshi Pal, and C. Shaha*. Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death. J. Biol. Chem, 281: 2133 – 2143 (2006).
- D.P. Mishra and C.Shaha* Estrogen induced spermatogenic cell apoptosis occur via the mitochondrial pathway: role of superoxide and nitric oxide. J. Biol. Chem, 280: 6181 – 6196 (2005).
- A. Mehta and C. Shaha*. Apoptotic death in Leishmania donovanipromastigotes in response to respiratory chain inhibition: complex II inhibition results in increased pentamidine cytotoxicity. J. Biol. Chem.,279: 11798 – 11813 (2004).
- G. Sudhandiran and C. Shaha*. Antimonial induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovaniamastigotes. J. Biol. Chem. 278:25120-25132. (2003).
- R. Nair and C. Shaha*. Diethylstilbestrol induces rat spermatogenic cell apoptosis in vivo through increased expression spermatogenic cell Fas/FasL system. J. Biol. Chem. 278:6470-6481 (2003).
- S.B.Mukherjee, M. Das, G. Sudhandiran and C. Shaha*. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovanipromastigotes. J. Biol. Chem. 277:24717-27 (2002).
- Manika Das, Sikha Bettina Mukherjee and C. Shaha*. Hydrogen peroxide induces apoptosis-like death in Leishmania donovanipromastigotes. J. Cell. Science, 114: 2461-9 (2001).