National Institute of Cholera and Enteric Diseases

Indian Council of Medical Research
Department of Health Research, Ministry of Health and Family Welfare, Government of India
WHO Collaborating Centre for Research and Training on Diarrhoeal Diseases

NICED : Scientists

Dr. Santasabuj Das

Dr. Santasabuj Das

Dr. Santasabuj Das is currently appointed as Scientist D at National Institute of Cholera and Enteric Diseases (NICED), Kolkata. He is also in-charge of the Biomedical Informatics Center of ICMR at NICED and the Biosafety Officer of the institute. Dr Das graduated in medical sciences (MBBS) in 1989 from the University of Calcutta and completed post-graduation (MD, General medicine) in 1996 from the same university. His post-doctoral training includes senior residency (clinical) at the Department of Clinical Immunology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow (1998) and post-doctoral fellowships at National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India (1998-2000); Kimmel Cancer Centre, Thomas Jefferson University, Philadelphia, PA, USA and Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA, USA. During the early part of his research career, Dr Das worked on the role of Notch signaling in cervical carcinogenesis and transcriptional regulation of MHC Class II molecules. Susequently, he studied the role of Tpl2, an upstream MAPKinase, in the pro-inflammatory cytokine (TNF-a and IL-1b)-induced signal transduction pathways.

Dr Das joined NICED in January, 2005 and initiated research on several aspects of the mucosal innate immune responses. His group is studying the regulation of cationic antimicrobial peptide release from the intestinal epithelial cells by enteric pathogens and host gene expression by bacterial motility protein flagellin. Studies to identify new virulence factors of Salmonella typhi and to explore the role of microRNAs in the pathogenesis of hepatitis B and HIV-1 infection are also underway. Dr. Das has 2 PhD students at present and he is the principal investigator of 4 extramural projects, 2 each from the Indian and international funding agencies. He has 5 publications in reputed international journals.

General Information
Name Dr. Santasabuj Das
Educational Qualification M.D. (General Medicine)
Designation Scientist E
Division Clinical Medicine
Specialization Molecular immunology and signal transduction
Date of joining ICMR 28th January 2005
Email : dasss@icmr.org.in

Profile

Professional Experience

I graduated in medical sciences (MBBS) in 1989 from the University of Calcutta and completed my post-graduation (MD, General Medicine) in 1996 from the same university. After a brief exposure to the basic research in immunology at Indian Institute of Chemical Biology, Kolkata, India, I joined the Department of Clinical Immunology at Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow, India as a senior resident (clinical) and worked there for about one year. I was involved in the diagnosis and management of patients suffering from autoimmune diseases and immune cell (hematological) malignancies. My career in laboratory research started at National Center for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR), Bangalore, India where I joined as a visiting post-doctoral fellow in late 1998. During my one and a half years of stay at NCBS, I worked on the role of Notch signaling in cervical carcinogenesis. I moved to USA for further post-doctoral training in the year of 2000 and joined the laboratory of Prof. Philip N. Tsichlis, the Director of the Basic Sciences Division at Kimmel Cancer Centre, Thomas Jefferson University, Philadelphia, Pennsylvania. I worked there on the transcriptional regulation of MHC Class II genes and showed that a particular domain of the transcription factor Tvl-1/RFXANK is required for the formation of a stable RFX transcriptome. During the later part of my post-doctoral training at the Molecular Oncology Research Institute under Tufts-New England Medical Center, Boston, Massachusetts, I studied the role of Tpl2, an upstream MAPKinase, in the pro-inflammatory cytokine (TNF-? and IL-1?)-induced signal transduction. Our study proved that Tpl2-mediates the activation of MAPKinases and NF-?B by TNF-? and IL-1?-induced signals in a cell-type and stimulus specific manner and that both the adaptor molecules TRAF2 and RIP-1 are required for transduction of TNF-? signals by Tpl2. I was also a co-investigator in the studies that showed that TNF-?-induced Tpl2 activating signals are also mediated by tyrosine kinase syk and Tpl2 is critically important in the pancreatic and lung inflammation during acute pancreatitis.

Research Interests

Small Cationic Antimicrobial peptides (AMPs): Regulation and Function

Small cationic endogenous peptides with antimicrobial properties form a critical component of the host innate immune system and protect the body from pathogens that invade through the mucosal surfaces. In addition to direct microbicidal activities against a broad range of organisms, AMPs possess pleotrophicimmunomodulatory functions, which protect the host from pathogenic infections as well as a number of autoimmune, inflammatory and neoplastic diseases. While newer functions have been described recently, published reports suggest that downregulation of the AMPs may serve as an efficient mode of immune evasion by the mucosal pathogens and perhaps tumours. Both natural and synthetic AMPs have been proposed as exciting novel therapeutic agents for infectious and non-infectious diseases. A particularly useful approach may be to induce the production of endogenous peptides. We are studying the regulatory mechanisms behind AMP production and their modulation by intestinal pathogens. Synthetic peptides targeting microbial virulence factors are also under investigation.

Salmonella Typhi: Virulence Mechanisms and Vaccine Development

Salmonella Typhi poses significant threat to public health worldwide and the infection is endemic in parts of India. While pathogenesis of the disease (typhoid or enteric fever) is incompletely understood, treatment failures are not uncommon due to drug resistance. This is further complicated by the limited effectiveness of the currently available vaccines, particularly in very young children where prevalence of the disease is increasing. This necessitates further understanding of pathogenesis and identification of new drug / vaccine targets. More than half of all S. Typhi genes are currently un-annotated.We employed computational approaches coupled with experimental validation to functionally characterize genes with potential role in the pathogenesis of S. Typhi.Our experiments involved the use of mutant and complemented bacteria and the purified recombinant proteins in vitro (cell line based experiments) and in vivo (iron overload mouse model of S. Typhi developed in the lab). We have also identified novel candidates for the development of subunit vaccines.

Indigenous Probiotics: Role in regulatory immune responses

Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Protection is observed against various infectious and non-infectious diseases, and mainly achieved through modulation of the host immune responses. We screened indigenous probiotic strains on the basis of their ability to generate regulatory responses in the intestine, which would help to develop an improved therapeutic strategy against autoimmune and inflammatory disorders. Several strains induced significant numbers of CD103+tolerogenic dendritic cells (DCs) and CD4+CD25+FoxP3+ T-regulatory cells, in addition to regulatory cytokines/chemokines (IL-10 and TGF- ß) in the mouse intestine and protected the animals against colitis induced by trinitrobenzene sulfonic acid (TNBS) (a model for inflammatory bowel disease) and SalmonellaTyphimurium-induced enterocolitis. We are also investigating the probiotics-derived molecules and the underlying mechanisms responsible for intestinal tolerogenic responses.

Bioinformatics:

Computational prediction and network analysis of host-pathogen interactions, molecular modeling and drug designing, comparative genomics, development of cholera portal.

Projects

Intramural

  • Host-pathogen interactions in human Salmonellaentericaserovar Typhi infections (September, 2014-August, 2017).
  • Studies on the development of T-regulatory responses in the intestine and their role in mitigating intestinal inflammation (September, 2014-August, 2017).

Extramural

Ongoing

  • Studies on immune responses elicited by candidate peptide vaccines and polysaccharide-peptide conjugate vaccines against Salmonella entericaserovars Typhi and Paratyphi infections(Funding agency: Council of Scientific and Industrial Research, Government of India; Duration: 1st January, 2015-31st December, 2017).
  • Study of mechanism of probiotic action in persistent diarrhea in children caused by enteroaggregative E.coli - using a mouse model (Funding agency: Indian Council of Medical Research, Government of India; Duration: 1st November, 2014-31st October, 2017).
  • Second phase of Task Force Biomedical Informatics Centre of ICMR (Funding agency: Indian Council of Medical Research, Government of India; Duration: 1st March, 2013-28th February, 2018).
  • Development and pre-clinical studies on safety and immunogenicity of novel candidate vaccines against Salmonella enterica serovar Typhi and Paratyphi (Funding agency: Department of Biotechnology, Government of India; Duration: 1st April, 2012-30th November, 2015).
  • Studies on the Regulation of Antimicrobial Peptide Expression and Their Role in Mixed and Opportunistic Infections of the Gut (Funding agency: Okayama University, Japan; Duration: 1st April, 2010-31st March, 2015).

Completed

  • Role of Toll-Like and NOD Receptors in Probiotics-Induced Mucosal Toleregenicity(Funding agency: Department of Biotechnology, Government of India; Duration: 1st June, 2011-31st May, 2014).
  • Biomedical Informatics Center of ICMR (Funding agency: Indian Council of Medical Research, Government of India; Duration: 1st July, 2006-30th June, 2012).
  • A Study on Differentiation-induced Regulation of the Immune Response Related Genes in the Intestinal Epithelial Cells (Funding agency: Indian Council of Medical Research, Government of India; Duration: 1st November, 2007-31st October, 2010).
  • Identification and Distribution of HIV-1 Encoded MicroRNAs in North-east Indian Population (Funding agency: Indian Council of Medical Research, Government of India; Duration: 1st June, 2007-31st May, 2010).
  • A Study on the Regulation of Antimicrobial Peptide Expression in the Intestinal Epithelial Cells (Funding agency: Okayama University, Japan; Duration: 1st April, 2007-31st March, 2010).

Ph.D. Students:

Past:

  • Dr. Krishnendu Chakraborty, PhD (Currently: Postdoctoral Fellow, Pittsburgh University, USA)
  • Dr. Subhamoy Ghosh, PhD (Currently: Postdoctoral Fellow, University of California, USA)

Present:

  • Mr. TheyaNagaraja (SRF:DBT project)
  • Ms. PujariniDatta (SRF: INSPIRE Fellow, DST)
  • Mr. Bhupesh Kumar Thakur (SRF: DBT project)
  • Ms. Atri Ta (SRF: Okayama University Project)
  • Mr. NirmalyaDasgupta (SRF: ICMR)
  • Mr. Asim Biswas (SRF: CSIR)
  • Mr. Sayan Das (SRF: CSIR)

Project Scientists/Project Fellows/Technical Officer:

Past:

  • Dr. SurajitBasak, Scientist II (Currently: Assistant Professor, Tripura University)
  • Dr. Paltu Kumar Dhal, Scientist II (Currently: Assistant Professor, Jadavpur University, Kolkata)

Present:

  • Dr. PiuSaha(DST Woman Scientist)
  • Dr. Ayan Lahiri (Research Associate: CSIR Project)
  • Dr. AmitaBarik (Scientist II: ICMR project)
  • Mr. Rahul ShubhraMondal (Scientist I: ICMR project)
  • Ms. RimiChowdhuri (Research Assistant: DBT project)
  • Mr. Ranjan Kumar Barman (Research Assistant: ICMR project)
  • Mr. Ananda Pal (Technical Officer: permanent staff)

Awards

  • National Bioscience Award for Career Development, 2011 (Department of Biotechnology)
  • Fulbright-Nehru Senior Research Fellowship, 2012.
  • BioAsia Innovation Award, 2015 to Rahul ShubhraMondal.
  • Best Poster Award to PiuSaha at the 2nd Annual conference of the Probiotic Association of India, 2014.
  • International Travel Support from DST, India toRahul ShubhraMondalto attend the 5th ACM Conference atCalifornia, USA, 2014.
  • Young Investigator Award to Bhupesh Kumar Thakur at the Yakult(India) Probiotics Meeting, 2014.
  • Best Poster Award to TheeyaNagaraja at the International Conference on Host-pathogen Interaction at NIAB, Hyderabad, 2014.
  • Best Poster Award to Rahul ShubhraMondal at the Conference on Recent Advances in Computational Drug Design at IISc, Bangalore, 2013.
  • Best Poster Award to PiuSaha at IMMUNOCON, 2013.
  • Best Poster Award to Bhupesh Kumar Thakurat the 1st Annual conferenceof the Probiotic Association of India, 2012.
  • Prof. Awtar Krishnan Prize to Bhupesh Kumar Thakur on Flowcytometry at NCBS, Bangalore, 2012.
  • Cytometrist of the Year Award to PiuSaha at the 5th Annual meeting of the Cytometriy Society, India, 2011.
  • InternationalTravel Supportfrom DSTto Krishnendu Chakraborty from DST, India to attend theKeystone Symposia at Trinity College, Dublin, Ireland, 2010.

Memberships

  • American Society of microbiology (contributing member)
  • Probiotic Association of India (life member)
  • Molecular Immunology Forum (nominated member)
  • Society of Biological Chemists, India (life member)
  • Indian Science Congress Association (life member)

Publications

2017

  1. Dasgupta N., B. K. Thakur, A. Ta, P. Dutta, and S. Das. 2017. Suppression of Spleen Tyrosine Kinase (Syk) by Histone Deacetylation Promotes, Whereas BAY61-3606, a Synthetic Syk Inhibitor Abrogates Colonocyte Apoptosis by ERK Activation. J Cell Biochem. 118(1):191-203. Pubmed

2016

  1. Thakur B. K., N. Dasgupta, A. Ta, and S. Das. 2016. Physiological TLR5 expression in the intestine is regulated by differential DNA binding of Sp1/Sp3 through simultaneous Sp1 dephosphorylation and Sp3 phosphorylation by two different PKC isoforms. Nucleic Acids Res. 2016 Jul 8;44(12):5658-72 Pubmed
  2. Thakur B. K., P. Saha, G. Banik, D. R. Saha, S. Grover, V. K. Batish, and S. Das. 2016. Live and heat-killed probiotic Lactobacillus casei Lbs2 protects from experimental colitis through Toll-like receptor 2-dependent induction of T-regulatory response. Int Immunopharmacol. 36:39-50 Pubmed
  3. Parida S, I. Pal, A. Parekh, B. Thakur, R. Bharti, S. Das, and M. Mandal. 2016. GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling. Cell Death Dis.;7:e2154 Pubmed
  4. Saha P, C. Manna, S. Das, and M. Ghosh. 2016. Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi. Sci Rep. 2016 Feb 19;6:21305 Pubmed
  5. Datta P, S. Das. 2016. Mammalian antimicrobial peptides: promising therapeutic targets against infection and chronic inflammation. Curr. Top. Med. Chem. 16(1):99-129. Pubmed

2015

  1. Das S and B. K. Thakur. 2015. Mucosal immune system of the respiratory tract: regulation of tolerance and immune response. The Pulmo-Face XV(2): 61-70.
  2. Mandal R. S and S. Das. In silico approach towards identification of potential inhibitors of Helicobacter pyloriDapE. J BiomolStructDyn.2015 Jul.33(7):1460-73 Pubmed
  3. Dasgupta N, B. K. Thakur, A. Ta A and S. Das. 2015. Caveolin-1 is transcribed from a hypermethylated promoter to mediate colonocyte differentiation and apoptosis.Exp Cell Res. 2015 Jun 10;334(2):323-36 Pubmed
  4. Banerjee R, S.Das, S.Basak. Similarity of currently circulating H1N1 virus with the 2009 pandemic clone: Viability of an imminent pandemic. Infection, Genetics and Evolution. 2015 Jun; 32:107-112. Pubmed
  5. Chowdhury R, R. S. Mandal, A. Ta and S. Das. An AIL family protein promotes Type Three Secretion System-1 independent invasion and pathogenesis of Salmonella entericaserovar Typhi. Cell Microbiol. 2015 Apr. 17(4):486-503 Pubmed
  6. Nagaraja T, A. Ta, S. Das, R. S. Mandal, O. Chakrabarti, S. Chakrabarti, A. N. Ghosh and S. Das. An Inducible and Secreted Eukaryotic-like Serine/Threonine Kinase of Salmonella Typhi Promotes Intracellular Survival and Pathogenesis. 2015. Infect Immun. 83(2):522-33 Pubmed
  7. Barman R. K., T. Jana, S. Das, S. Saha. 2015. Prediction of intra-species protein-protein interactions in enteropathogens facilitating systems biology study. PLoS One. 10(12):e0145648. Pubmed
  8. Mandal R. S., S. Saha, S. Das. 2015. Metagenomic surveys of gut microbiota. Genomics, Proteomics Bioinformatics 13(3):148-158. Pubmed

2014

  1. Bhowmick S, M. Malar, A. Das, B. K. Thakur, P. Saha, S. Das, H. M. Rashmi, V. K. Batish, S. Grover and S. Tripathy. 2014. Draft Genome sequence of Lactobacillus casei Lbs2. Genome Announc.2(6): e01326-14 Pubmed
  2. Barman RK, S. Saha, S Das. 2014. Prediction of interactions between viral and host proteins using supervised machine learning methods. PLoS ONE. 9(11):e112034 Pubmed
  3. Dhal P. K, R. K Barman, S. Saha and S. Das. 2014. Dynamic Modularity of Host Protein Interaction Networks in Salmonella Typhi Infection. PLoS One. 9(8):e104911 Pubmed
  4. Bhattacherjee A, R.S. Mandal, S. Das, S. Kundu. 2014. Sequence and 3D structure based analysis of TNT degrading proteins in Arabidopsis thaliana. J Mol Model. 20(3):2174. Pubmed

2013

  1. Rajendra Kumar Labala, Santasabuj Das, and Surajit Basak 2013. ASRDb: A comprehensive resource for archaeal stress response genes. Bioinformation. 9: 650-655. Pubmed

2012

  1. Dasgupta A., R. Banerjee, S. Das and S. Basak. 2012. Evolutionary perspective on the origin of Haitian cholera outbreak strain. J Biomol Struct Dyn. 30: 338-46. Pubmed
  2. Banerjee R, A. Roy, F. Ahmad, Das S, S. Basak. 2012. Evolutionary patterning of hemagglutinin gene sequence of 2009 H1N1 pandemic. J Biomol Struct Dyn. 29: 733-742. Pubmed

2011

  1. Ghosh S., K. Chakraborty, T. Nagaraja, S. Basak, H. Koley, S. Dutta, U. Mitra and S. Das. 2011. An adhesion protein of Salmonella enterica serovar Typhi is required for pathogenesis and potential target for vaccine development.
    Proc Natl Acad Sci U S A. 108: 3348-3353. Pubmed

2010

  1. Roy N, S. Barman, A. Ghosh, A. Pal, K. Chakraborty, S. Das, D. R. Saha, S. Yamasaki and H. Koley. 2010. Immunogenicity and protective efficacy of Vibrio cholerae outer membrane vesicles in rabbit model. FEMS Immunol Med Microbiol. 60: 18-27. Pubmed
  2. Bhadra R. K., S. Das and G. B. Nair. 2010. Immunological basis for Immunization: Cholera. WHO/IVB/ISBN 978 92 4 159974 0, pp.1-31. Pubmed

2009

  1. Sinha, N. K., A. Roy, B. Das, S. Das and S. Basak. 2009. Evolutionary complexities of swine flu H1N1 gene sequences of 2009. Biochem Biophys Res Commun. 390: 349-51. Pubmed
  2. Chakraborty, K., P. C. Maity, A. K. Sil, Y. Takeda and S. Das. 2009. cAMP stringently regulates human cathelicidin antimicrobial peptide expression in the mucosal epithelial cells by activating cAMP-response element-binding ptotrin, AP-1, and Inducible cAMP early repressor. J Biol Chem. 284:21818-21827. Pubmed
  3. Basak, S., R. Banerjee, I. Mukherjee, S. Das. 2009. Influence of domain architecture and codon usage pattern on the evolution of virulence factors of Vibrio cholerae. Biochem Biophys Res Commun. 379: 803-805. Pubmed

2008

  1. Basak, S., I. Mukherjee, M. Choudhury and S. Das. 2008. Unusual codon usage bias in low expression genes of Vibrio cholerae. Bioinformation. 3: 213-217. Pubmed
  2. Chakraborty, K., S. Ghosh, H. Kole, A. K. Mukhopadhyay, T. Ramamurthy, D. R. Saha, D. Mukhopadhyay, S. Roychowdhury, T. Hamabata, Y. Takeda and S. Das. 2008. Bacterial exotoxins downregulate cathelicidin (hCAP18/LL37) and human defensin 1 (HBD-1) expression in the intestinal epithelial cells. Cell Microbiol. 10: 2520-2537. Pubmed
  3. Chakraborty, K., S. Ghosh, H. Kole, A. K. Mukhopadhyay, T. Ramamurthy, D. R. Saha, D. Mukhopadhyay, S. Roychowdhury, T. Hamabata, Y. Takeda and S. Das. 2008. Bacterial exotoxins downregulate cathelicidin (hCAP18/LL37) and human defensin 1 (HBD-1) expression in the intestinal epithelial cells. 2008. (In Press). Pubmed

2007

  1. Van Acker, G. J., G. Perides, E. R. Weiss, S. Das, P. N. Tsichlis and M. L. Steer. 2007. Tumor progression locus-2 is a critical regulator of pancreatic and lung inflammation during acute pancreatitis. J. Biol Chem. 282: 22140-9. Pubmed

2006

  1. Ghosh, A., D. R. Saha, K. M. Hoque, M. Asakuna, S. Yamazaki, H. Koley, S. Das, M. K. Chakraborty and A. Pal. 2006. Enterotoxigenicity of 45kDa matured and 35kDa processed forms of hemagglutinin protease purified from a cholera toxin gene negative Vibrio cholerae non-O1non-O139 strain. Infect Immun. 74: 2937-46. Pubmed
  2. Eliopoulos, A. G., S. Das and P. N. Tsichlis. 2006. The tyrosine kinase Syk regulates TPL2 activation signals. J. Biol Chem. 281: 1371-80. Pubmed

2005

  1. Das, S., J. Cho, I. Lambertz, M. A. Kelliher, A. G. Eliopoulos, K. Du and P. N. Tsichlis. 2005. Tpl2/Cot Signals Activate ERK, JNK, and NF-?B in a Cell-type and Stimulus-specific Manner. J. Biol Chem. 280: 23748-57. Pubmed

2002

  1. Das, S., J. H. Lin, J. Papamatheakis, Y. Sykulev and P. N. Tsichlis. 2002. Differential splicing generates Tvl-1/RFXANK isoforms with different functions. J. Biol Chem. 277: 45172-80. Pubmed

Patents

  1. A novel protein of Salmonella Typhi as a probable subunit of vaccine (506/DEL/2010).
  2. A novel multi-serotype Shigella vaccine based on outer membrane vesicles (MOMV) (Application no. 1652/DEL/2013 (Indian patent); PCT/IN2014/000369).
  3. Designed antisepsis and cell penetrating peptide. (462/DEL/2015).

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