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Research Interests

Our lab’s research interests are primarily to understand cell death mechanisms in unicellular (Leishmania) and multicellular (cancer) biological systems towards development of improved therapeutics. Besides cell biology techniques, we apply a combination of biophysical tools like high resolution microscopy approaches such as Transmission Electron Microscopy, Scanning Electron Microscopy and Laser Scanning Confocal Microscopy for investigating the morphological and physiological effects of lead molecules and drug candidates.

Apoptosis, a key mechanism for inducing programmed cell death (PCD) has been demonstrated in kinetoplastid protozoans like Leishmania (causal organism for Leishmaniasis, a tropical neglected vector borne disease) and is no longer considered to be limited to multi-cellular organisms. Although Leishmania share many biochemical markers with metazoan apoptosis, the molecular machinery involved differs considerably and is not well understood. These parasites have special organelles involved in essential metabolic pathways with steps differing from those found in mammalian hosts. A better understanding of mechanistic machinery of apoptosis-like PCD in protozoan protists thus would prove immensely beneficial in designing rational chemotherapeutic interventions in a target-dependent manner. In our ongoing efforts to identify and understand the mode of action of new and effective leishmanicidal agents, several synthetic and natural compounds are currently being evaluated in our laboratory.

We are also interested in basic processes involved in autophagy, understanding how it regulates cell death in cancer cells and understanding how it can be utilized for improved therapeutic outcome in cancer. Essentially a mechanism for recycling damaged organelles, autophagy is considered to be a double-edged sword in cancer since depending on the cellular milieu; it can play either a pro-death or pro-survival role. While autophagic cell death contributes to the efficacy of anti-cancer drugs, a pro-survival role contributes to chemo-resistance. There exists significant cross-talk of molecular signaling between apoptosis and autophagy since they share common signaling molecules in cancer cells. Therefore, it is critical to understand how autophagy can be modulated for designing targeted cancer therapies which are currently in focus for anti-cancer drug development.

Other ongoing collaborative projects include morphological characterization of drug delivery systems and biological nanostructures and macromolecular complexes using electron microscopy. We are also involved in the development of novel fluorescent probes for cell imaging applications.

image01  Recent Selected Publications:

  • 1) Hasanain M, Bhattacharjee A, Pandey P, Ashraf R, Singh N, Sharma S, Vishwakarma AL, Datta D, Mitra K*, Sarkar J*. α-Solanine induces ROS-mediated autophagy through activation of endoplasmic reticulum stress and inhibition of Akt/mTOR pathway. Cell Death Dis. 2015 Aug 27;6:e1860. doi:10.1038/cddis.2015.219. PubMed PMID: 26313911

  • 2) Bhaskar, Mitra K, Kuldeep J, Siddiqi MI, Goyal N*. The TCP1γ subunit of Leishmania donovani forms a biologically active homo-oligomeric complex. FEBS J. 2015 Dec;282(23):4607-19. doi: 10.1111/febs.13521. Epub 2015 Oct 26. PubMed PMID:26395202.

  • 3) Kathuria M, Bhattacharjee A, Sashidhara KV, Singh SP, Mitra K*. Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene. Antimicrob Agents Chemother. 2014 Oct;58(10):5916-28. doi: 10.1128/AAC.02459-14. Epub 2014 Jul 28. PubMed PMID: 25070112; PubMed Central PMCID: PMC4187897

  • 4) Goel A*, Sharma A, Kathuria M, Bhattacharjee A, Verma A, Mishra PR, Nazir A, Mitra K*. New fluoranthene FLUN-550 as a fluorescent probe for selective staining and quantification of intracellular lipid droplets. Org Lett. 2014 Feb 7;16(3):756-9.