Dr. Sanjeev Das
Research Interest:
The focus of the laboratory is to explore the regulatory milieu of tumor suppressor proteins. The lab also has an active interest in tumor cell metabolism. We employ diverse methodologies to examine the role of regulatory networks and metabolic processes in tumorigenesis.
Summary of Research:
Cancer is a leading cause of death worldwide. It is a disease caused when a population of cells divide out of control, invade and destroy adjacent tissues, and often spread to distant organs through a process called metastasis. p53 is one of the most important tumor suppressors in the cell and often referred to as ‘‘the cellular gatekeeper for growth and division’’. In unstressed cells, p53 is maintained at very low levels. In response to various intracellular and extracellular stresses, such as damages to DNA integrity, hypoxia, and oncogene expression, p53 is rapidly stabilized and activated. The activated p53 mainly functions as a sequence-specific DNA-binding transcription factor to regulate a large number of target genes. These genes mediate cell-cycle arrest, apoptosis, senescence, differentiation, DNA repair, inhibition of angiogenesis and metastasis. The transcriptional activity of p53 is critical to its function as a tumor suppressor. This is highlighted by the fact that approximately 50% of human cancers contain a mutation in the p53 gene. Among them, more than 80% are located in the p53 DNA-binding domain (DBD), which abrogates the p53 transcriptional activity. The ever expanding repertoire of p53 target genes include pro-arrest genes like p21, 14-3-3s, pro-apoptotic genes such as Bax, Noxa, Puma, genes involved in DNA repair like p53R2, MSH2 etc. Emerging data suggest that p53 plays an important role in regulating cellular metabolism. Several p53 target genes have been identified including TIGAR, Sco2, PGM, sestrin1 and sestrin2 etc. which play a key role in metabolic processes. These novel targets of p53 facilitate the homeostatic regulation of energy production and coordinate the rate of ROS (Reactive Oxygen Species) biogenesis and clearance. Our interest is to comprehend the role played by p53 in metabolic stress response. We would like to unravel the plethora of genes regulated by p53 in response to metabolic stress. Microarray, RNAi, and functional assay based approaches are being used to identify and characterise novel p53 target genes. In addition we would like to identify other proteins with which p53 interacts to initiate the stress response process using protein-protein interaction based approaches like yeast two hybrid and immunoprecipitation/mass spectroscopy. Thus the overall goal is to understand what and how the final cellular outcome of survival, senescence or apoptosis is achieved in response to metabolic stress.
Group Members:
Ph.D. Students: Madhurima Ghosh, Rohini Tamang, Witty Tyagi and Anita Nandi
Technical Assistant: Arun Lal
Awards:
• 2018 Fellow, National Academy of Sciences, India
• 2017 Shanti Swarup Bhatnagar Prize for Biological Sciences, Council for Scientific and Industrial Research, Govt. of India
• 2017 Prof. Umakant Sinha Memorial Award, Indian Science Congress Association, India
• 2016 Shakuntala Amir Chand Prize, Indian Council of Medical Research, India
• 2016 Prof. B. K. Bachhawat Memorial Young Scientist Lecture Award, National Academy of Sciences, India
• 2015 National Bioscience Award for Career Development, Department of Biotechnology, Govt. of India
• 2014 NASI-SCOPUS Young Scientist Award, National Academy of Sciences, India and Elsevier
Publications:
- Madhurima Ghosh and Das S*. PRAMEF2-mediated dynamic regulation of YAP signalling promotes tumorigenesis (2021). Proc Natl Acad Sci USA, 118, e2105523118.
- Kumari R, Deshmukh RS and Das S*. Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis (2019). Nature Communications, 10, 4255.
- Deshmukh RS, Sharma S and Das S*. Cyclin F-dependent degradation of RBPJ inhibits IDH1R132H-mediated tumorigenesis (2018). Cancer Research, 78, 6386-6398.
- Kohli S, Bhardwaj A, Kumari R and Das S*. SIRT6 is a target of regulation by UBE3A that contributes to liver tumorigenesis in an ANXA2-dependent manner (2018). Cancer Research, 78, 645-658.
- Bhardwaj A and Das S*. SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions (2016). Proc Natl Acad Sci USA,113, E538-E547.
- Satija YK and Das S*. Tyr99 phosphorylation determines the regulatory milieu of tumor suppressor p73 (2016).Oncogene,35, 513-527.
- Sen N, Kumari R, Singh MI and Das S*. HDAC5, a key component in temporal regulation of p53-mediated transactivation in response to genotoxic stress (2013). Molecular Cell,52, 406-420.(Featured Article)
- Sen N, Satija YK and Das S*. PGC-1a, a key modulator of p53, promotes cell survival upon metabolic stress (2011). Molecular Cell,44, 621-634.(Featured Article)
* as corresponding author
Faculties
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