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:

The area of my current research interest is mucosal innate immune responses.

1. Regulation of antimicrobial peptide (AMP) expression: AMPs are small cationic proteins that form a critical component of the host innate immune system and protect the body from pathogens that invade through the mucosal surfaces. Published reports suggest that downregulation of the AMPs may serve as an efficient mode of immune evasion by the mucosal pathogens; however, neither the pathogen-derived factors nor the mechanism of downregulation is currently known. We have recently shown that cholera toxin and LT may transcriptionally downregulate cathelicidin and human -defensin 1 expression in the intestinal epithelial cells by inducing multiple intracellular signal transduction pathways (In press). We are currently trying to identify the transcription factors that regulate the basal or inducible production of the AMPs. Studies on AMP regulation by other PAMPs like bacterial flagellin and viral double-stranded RNAs are also underway.
    
2. Pattern recognition receptor (PRR) signaling: PRRs (TLRs and NLRs) have been identified as the key molecules for innate recognition of pathogenic microorganisms. Bacterial motility protein flagellin binds to TLR5 on the cell surface. Although the crystal structure of TLR5/flagellin interaction is not resolved, genetic and biochemical approaches have identified the interacting domains as well as several critical residues required for the interaction. However, the downstream signaling mechanisms have not been studied in detail. We have found that different intracellular signaling pathways are activated by flagellins of different origins. We are trying to identify the factors that determine the recruitment of specific signaling molecules. Simultaneously, we are dissecting the signaling pathways and subsequent regulation of gene expression.
    
3. Epithelial differentiation induced regulation of mucosal immune response: Considering the unique disposition of epithelial cells in the intestinal wall with gradually increased differentiation towards the lumen, epithelial differentiation may significantly contribute towards maintaining the intestinal homeostasis and simultaneously preventing the pathogens to invade the body. Studies published by different groups have shown that the expression of immune recognition receptors (eg, TLRs) as well as immune effector molecules (cytokines, chemokines, antimicrobial peptides etc) may be altered in the differentiated cells; however, the mechanisms remain largely unexplored. Using butyrate-induced epithelial differentiation model, we are studying transcriptional regulation of the genes that have significantly altered expression in the differentiated cells.
    
4. Host-pathogen interactions in human salmonella infection: The virulence factors described till date fail to account for the entire spectrum of human diseases that include both inflammatory diarrhea and enteric fever caused by the salmonella spp. Using bioinformatic and wet laboratory (genetic and biochemical) approaches as well as the animal models, we are trying to identify novel virulence factors of salmonella spp that infect humans and their role in the pathogenesis.
    
5. Role of microRNAs in chronic hepatitis and HIV/AIDS: microRNAs are small (18-25 nt) non-coding RNAs that have recently been identified to play a major role in gene regulation. Although, several HIV-1 and hepatitis B-encoded microRNAs have been described and host miRNA expression pattern has been proposed to be altered during infection with these viruses, the precise role of either host or virus-encoded miRNAs in the pathogenesis remains unexplored. We are trying to identify the miRNAs that may be involved in host-pathogen interaction during hepatitis B and HIV-1 infection.
    

Projects

Intramural :

1. Exploring the Mechanism of the Immunomodulatory Functions of Cholera Toxin

Extramural :

1. Biomedical Informatics Center of ICMR (Indian council of Medical Research)

2. Identification and Distribution of HIV-1 Encoded MicroRNAs in North-east Indian Population (Indian council of Medical Research)

3. A Study on Differentiation-induced Regulation of the Immune Response Related Genes in the Intestinal Epithelial Cells (Indian council of Medical Research)

4. A Study on the Regulation of Antimicrobial Peptide Expression in the Intestinal Epithelial Cells (Okayama University, Japan)

Pre-doctoral Students :

1. Mr. Krishnendu Chakraborty (Pre-doctoral)

2. Mr. Subhamoy Ghosh (Pre-doctoral)

3. Mr. Theya Nagaraja (Pre-doctoral)

4. Ms. Rima Tapadar (Pre-doctoral)

5. Ms. Pujarini Datta (Pre-doctoral

 Memberships /Fellowships:

Indian Science Congress Association (2005).