Mahadeb Pal
Ex-
Mahadeb Pal
Ex-, Division of Molecular Medicine
Research interests:
Major objectives in the lab include
-Finding small molecule modulators of HSF1 from natural sources and study their mode of actions to assess their cellular toxicity/potential therapeutic efficacy.
-Study control of HSF1 function in cells by biochemical approaches. We are interested to know the factors that collaborate with HSF1 under different cellular stressful environments.
-Finding small molecules from natural sources that would kill cancer cells of different organ origins with high specificity, and study their mode of actions to assess toxicity associated with using these molecules.
Contact:
| Address: |
Division of Molecular Medicine Centenary Campus Bose Institute P-1/12 C.I.T. Scheme VII-M Kolkata - 700054, India |
| E-Mail: | mahadeb[at]jcbose.ac.in |
| Phone: | +91-33-25693256 |
Research:
A normal cell can sense if a protein is misfolded or aggregated and take appropriate action to stay healthy. A healthy cell under this circumstance activates heat shock response (HSR), also called proteotoxic stress response (PSR) to upregulate the expression of genes encoding protein chaperones to refold the protein back to its native conformation. In case it is not appropriate- the protein is degraded by activation of processes such as proteasome and or autophagy pathway(s) to maintain a healthy cellular environment. The HSR dies down to inactive state as usual as the stress is neutralized or removed. A central regulator of HSR is the heat shock factor 1 (HSF1), a transcription activator. HSR upregulation is marked by activated state of cellular HSF1 protein. It has been shown by independent laboratories that cells in transformed as well as neurodegenerative states lose standard control over their HSF1 function. For example, cancer cells maintain a constitutively activated state of HSF1 and downregulation of HSF1 was shown to sensitize cancer cells. On the other hand the cells with a neurodegenerative condition as occur in diseases like Parkinson’s disease, being unable to sense the accumulation of protein aggregate, fail to upregulate HSF1 function. These cells die due to toxicity caused by the protein aggregate it accumulates. It has been found by independent investigators that forced upregulation of HSF1 or its target protein chaperone ameliorates the protein misfolding associated toxicity in animal model. Thus far however no specific small molecule activator/inhibitor of HSF1 has reached the clinic. To this end we have already isolated a compound (azadiradione) that activates HSF1 by direct interaction with the protein. This is the only compound thus far reported that activates HSF1 by interact interaction. We- in another project- are investigating how PSR links with cellular inflammation- a critical mediator of cellular transformation- have unearthed a unique mechanism. Projects are running well in the lab to isolate small molecules anticancer agents from natural sources based on studies with cell and animal models.
Publications:
Selected Publications
1.Paul, S., Ghosh, S., Mandal, S., Sau, S, and Pal, M. (2018) NRF2
transcriptionally activates the heat shock factor 1 promoter under oxidative
stress and affects survival and migration potential of MCF7 cells. J Biol
Chem. 2018 Oct 11. pii: jbc.RA118.003376 [Epub ahead of print]
2.Ali, A., Biswas, A. and Pal, M. (2018)
HSF1
mediated TNF-α production during proteotoxic stress response pioneers
proinflammatory signal in human cells. FASEB J. 2018 Oct
11:fj201801482R. doi: 10.1096/fj.201801482R. [Epub ahead of print]
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Recognition:
Teaching:
Students:
| Image | Name | Designation | Department | Campus | Contact number | |
|---|---|---|---|---|---|---|
 |
Hossainoor Rahaman Sareng | Senior Research Fellow | Division of Molecular Medicine | Centenary | hossainoorsareng@gmail.com |