Dr Santasabuj Das is currently appointed as Scientist E at the National Institute of Cholera and Enteric Diseases (NICED), Kolkata. He is also the principal investigator and coordinator of the Biomedical Informatics Center of ICMR at NICED. He has the academic and professional background in Clinical Medicine and is pursuing a full-time research career since 1998. He joined NICED as an independent investigator and a permanent employee in January 2005. His current research interest spans several areas of host responses to microorganisms (both pathogens and commensals) including immune responses and vaccine development. The major focus of his research is the pathogenesis of human Salmonella infections, development of subunit and conjugate vaccines against Salmonella Typhi and Paratyphi and the regulation of mucosal immune responses at the intestine during homeostasis as well as under disease conditions, such as intestinal infections and inflammatory bowel diseases. Dr Das extensively uses computational tools, in vitro and in vivo techniques and clinical materials to address his research questions. His laboratory has developed a novel mouse model of Salmonella Typhi infection. Using this model, his research has identified several virulence factors critical for the pathogenesis of Salmonella Typhi and developed a candidate subunit vaccine. His research has unearthed a number of novel signalling mechanisms that underlie pro-apoptotic and anti-cancer role of dietary fibres and regulate intestinal innate immune responses by regulating the expression of Toll-like receptors and small cationic antimicrobial peptides. His research has been funded by extramural grants from all the major funding agencies of the country (ICMR, DBT, CSIR, DST, DHR) as well as the Ministry of Education, Culture, Sports, Science and Technology of Japan and Japan Agency for Medical Research and Development. Dr Das has published 43 original research articles and 3 review articles in reputed international journals, 2 book-chapters and one WHO Module. His innovative research has been granted 2 international and one national patents. In recognition of his seminal contribution to the biomedical and health science research, he has been awarded the National Bioscience Award for Career Development, 2011 by the Department of Biotechnology, Government of India and Fulbright-Nehru Senior Research Fellowship, 2012. He is also an elected member of the West Bengal Academy of Science and Technology.
Dr Santasabuj Das is a medical graduate from the
University of Calcutta, Kolkata (MBBS, 1989). He
completed his post-graduation from the same university
(MD, General Medicine, 1996).
Worked briefly at the Division of Cellular Immunology, CSIR-Indian Institute of Chemical Biology, Kolkata as a Research Associate and then at the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow as a Senior Resident.
Worked as a Visiting Postdoctoral Fellow at the National
Center for Biological Sciences (NCBS), Bangalore from
1998-2000. The area of his research was Notch signaling
in cervical cancer.
Joined the laboratory of Dr. Philip N Tsichlis, Director of Basic Sciences, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA as a Postdoctoral Fellow in the year 2000. There he worked on transcriptional regulation of MHC class II genes.
Joined Dr. Tsichlis’s laboratory as a Postdoctoral Research Associate in 2002 after he took over the charge of the Director of Molecular Oncology Research Institute at Tufts University Medical Center at Boston, Massachusetts, USA. The focus of his research was to explore the role of Tpl2, an upstream mitogen-activated protein kinase in transducing the signals induced by pro-inflammatory cytokines like TNF-alpha and IL-1beta and in lung and pancreatic inflammation. Altogether, he spent nearly five years at Dr. Tsichlis’s laboratory and worked on the mechanisms underlying the development and progression of inflammatory diseases.
Salmonella Typhi: pathogenesis and vaccine development
Salmonella Typhi (S. Typhi), the etiologic agent for typhoid poses significant threat to public health, especially in the developing countries. This is contributed by poor knowledge about the disease pathogenesis, treatment failures due to multidrug resistance and unavailability of highly efficacious vaccines. We employed computational approaches coupled with experimental validation to identify novel virulence proteins that promote adhesion and invasion of S. Typhi to intestinal epithelial cells and phagosomal survival within macrophages. In addition, we have developed a protein subunit vaccine that showed significant promise in pre-clinical evaluation. Currently, we are studying the role of stringent response in the persistence of S. Typhi within host macrophages and the mechanisms contributing to the chronic carrier state of S. Typhi and the subsequent development of gall bladder cancer.
Cationic antimicrobial peptides (AMPs): regulation and function
Cationic AMPs are essential components of the innate immune system at the mucosal surfaces. They possess profound immunomodulatory functions in addition to direct microbicidal effects against a wide range of organisms and protect from infectious, autoimmune and neoplastic diseases. Despite significant therapeutic promise, AMPs have not been successfully used for systemic diseases till date, primarily due to problems related to therapeutic formulation and drug delivery. An alternate approach may be to modulate endogenous production of AMPs to cater their varying needs. We have explored several novel mechanisms underlying human cathelicidin production in the intestine and showed that these mechanisms may be exploited to effectively combat enteric infections and inflammations. Additionally, along with our collaborators, we have designed synthetic antimicrobial and immunomodulatory peptides for the treatment of intracellular pathogens and sepsis.
Regulation of intestinal homeostasis
Intestinal homeostasis is critical to maintain normal bacterial flora as well as protection from invading pathogens. Intestinal microflora confers health, while an altered flora (dysbiosis) has been associated with infections, inflammation, metabolic and neurological diseases and cancer. Among numerous factors, short chain fatty acids (SCFAs), especially butyrate derived from fermentation of dietary fibres by the microflora plays a central role in maintaining intestinal homeostasis. We have described novel mechanisms of butyrate functions, which include the regulation of expression of Toll like receptors (TLR5), tumour suppressor genes (caveolin 1) and oncogenes (Syk, PLK1). We have also studied the regulation of immune homeostasis of the intestine by Toll-like receptor signaling and restoration of homeostasis by probiotic bacteria for the treatment of intestinal inflammation.
Computational prediction and network analysis of host-pathogen interactions, molecular modeling and drug designing, immunoinformatics, comparative genomics, multiOMICS data analysis, designing and development of databases and webservers.
Ongoing (as principal Investigator)
Completed Completed (as principal Investigator)
For complete bibliography, please see: http://1.usa.gov/21gp5Ff