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Brief Profile of the Awardee


Dr Sanjeev Das

  • 2017
  • Biological Sciences
  • 27/08/1976
  • Cancer Biology
Award Citation:

Dr Das has made outstanding contributions in the area of cancer biology, which have provided novel mechanistic insights into the functioning of p53 and sirtuins.

Academic Qualifications:
Thesis and Guide details:
Details of CSIR Fellowship/ Associateship held, if any or from other sources/ agencies.
Significant foreign assignments:
(a) Significant contributions to science and/ or technology development by the nominee based on the work done in India during most part of last 5 years:
The major scientific contributions of Dr. Sanjeev Das are in the field of cancer biology. Dr. Das has worked extensively on understanding the regulatory milieu of tumor suppressors, the proteins that regulate diverse processes underlying tumorigenesis (Molecular Cell, 2011; Cell, 2007). The focus of Dr. Das's work in the last five years has been on p53 family of tumor suppressors and sirtuins. Using mass spectrometry based approaches, they identified various proteins with which p53 interacts to initiate the stress response process, one of them being HDAC5 (Histone Deacetylase 5). Their studies demonstrated that HDAC5 is a deacetylase that plays a key role in regulating p53 acetylation status, which has immense influence on its target selection. Thus HDAC5 plays a key role in modulating p53-mediated genotoxic stress response that augments prosurvival functions of p53 over apoptosis by promoting preferential transactivation of p53 proarrest and antioxidant target genes (Molecular Cell, 2013). This was the first study demonstrating the temporal regulation of a key p53 posttranslational modification that determines p53-mediated transactivation and cell fate decisions. Using proteomics approach, they also identified novel interacting proteins of the p53 family member p73 such as ubiquitin ligase TRIM28 and transcriptional coactivator Med15. They reported that TRIM28 polyubiquitylates p73 specifically in unstressed conditions, resulting in p73 degradation. Upon genotoxic stress p73 gets phosphorylated leading to abrogation of its interaction with TRIM28 resulting in p73 stabilization. Furthermore, the phosphorylated form of p73 specifically interacts with MED15 which serves as a transcriptional coactivator and promotes anti-metastatic functions of p73 (Oncogene, 2016). These findings enhance our understanding of the role of posttranslational modifications in p53 family-mediated response to chemotherapy. Furthermore, their studies have also revealed the molecular mechanisms underlying the tumor suppressor functions of sirtuin family member SIRT6. They mapped the SIRT6 interactome and characterized two key interacting proteins viz. PKM2 and UBE3A. They demonstrated that SIRT6 binds to and deacetylates nuclear PKM2 (Pyruvate kinase M2), a glycolytic enzyme with non-metabolic nuclear protein kinase and transcriptional coactivator functions. SIRT6-mediated deacetylation results in PKM2 nuclear export. They further identified exportin 4 as the specific transporter mediating PKM2 nuclear export. As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus SIRT6 suppresses PKM2 oncogenic functions. Furthermore, reduced SIRT6 levels correlate with elevated nuclear acetylated PKM2 levels in increasing grades of hepatocellular carcinoma (PNAS, 2016). On the other hand, UBE3A ubiquitylates SIRT6 leading to its proteasomal degradation thereby promoting aggressive tumor phenotype in hepatocellular carcinoma (Oncogene, 2017). These findings provide key insights into SIRT6 tumor suppressor functions and regulation. In conclusion, the work from Dr. Das's laboratory has led to a keen understanding of tumor suppressor proteins. His work provides mechanistic insights on regulatory and metabolic perturbations intrinsic to tumorigenesis. It also highlights the vulnerabilities in tumor cell biology which could be exploited for therapeutic interventions that bring about a positive clinical outcome.
(b) Impact of the contributions in the field concerned:
p53 is an attractive target in combating cancer due to the high potency of p53-mediated tumor suppression, including growth arrest and induction of apoptosis, inhibition of angiogenesis, as well as blocking invasion and metastasis. The work from Dr. Das's laboratory established that tight regulation of p53 posttranslational modifications is a key determinant of p53-mediated cell fate decisions. Through chemical genetics and high throughput screening based approaches small molecules can be developed to regulate the p53 modifying enzymes such as that p53 proapoptotic functions are potentiated. These can be combined with traditional chemo- and radiation therapy based regimens to increase their tumor clearance efficacy. New roles of p53 are immensely reshaping the multifarious facets of metabolism. Given the current understanding of tumor metabolism, there is an opportunity to generate a new class of anti-tumor drugs that target altered metabolism in cancer cells. There are differences between normal cell metabolism and cancer cell metabolism that provide clinically relevant therapeutic windows. The findings from Dr. Das's laboratory help in identifying the therapeutic windows for targeting cancer cell metabolism due to the addiction of cancer cells to specific nutrients to support deregulated cell growth programs enforced by cancer genes. Elucidating the pathways by which p53 coordinates metabolic adaptation could establish new therapeutic targets in cancers that express wild-type p53. The relative contribution of each of the many p53 metabolic target genes might differ according to cell type, stress signal and other circumstances, and it is quite likely that not all p53 targets will be equally important to the final response. Furthermore, whether a p53 target gene responds to high or low stress is also likely to depend very much on the tissue in which the response is activated, and on the type of stress signal activating it. However, increased understanding of the role of p53 in metabolism will provide a rich harvest of new therapeutic targets. The function of the guardian of the genome, p53, is often compromised in cancers. Due to the high structural and functional homology to p53, regulation of p73 function represents a unique approach for targeted cancer therapy. p73 can potentially be induced or activated to replace inactive p53 for induction of cell cycle arrest/apoptosis. The work from Dr. Das's laboratory enhances the understanding of p73 interactome. It delineates the mechanisms determining p73 protein stability and functions. This enables the development of new cancer therapeutics for cases where p53 functions are compromised and p73 can be activated to bring about tumor regression. Previous studies have demonstrated that SIRT6 plays critical roles in maintaining genomic stability and metabolic homeostasis, thereby impacting several pathways pertinent to cancer, metabolism and aging. Dr. Das's work throws light on SIRT6 regulation and the crosstalk between SIRT6 and other metabolic regulators. His findings present an in-depth analysis of transcriptional regulation of metabolic processes and provide a robust platform for further studies to fully discover the activities of this important chromatin protein in mammalian pathophysiology. Since metabolic reprogramming is intrinsic to tumorigenesis, his work helps to understand how modulating SIRT6 activity could provide therapeutic benefits under conditions of metabolic imbalance observed in tumors.
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The Awardee a fellow of the Indian National Science Academy/Indian Academy of Sciences/National Academy of Sciences/Others:
The Awardee delivered invited lecture(s) in India/abroad and/or chaired any scientific Internatiional Conference Symposium:
List of Awardee's 10 most significant publications.
List of Awardee's 5 most significant publications during the last 5 years
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Contact Details

  • Molecular Oncology Laboratory
    National Institute of Immunology
    Aruna Asaf Ali Marg
    New Delhi - 110067
    Delhi INDIA
  • 011 2670 3702
  • 011 2674 2125
  • sdas[at]nii[dot]ac[dot]in
23 Oct 2017, http://ssbprize.gov.in/Content/Detail.aspx?AID=527