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