Research Interests Innate immunity of an organism is the inborn protection against invading pathogens. Because it is inborn, and entrusted with the protection of host from a vast array of previously unknown invaders, the innate immune system generates a generalized alert response upon pathogen detection. This alert is chemically mediated by a class of molecules called Cytokines. A critical task for this host protection system is to distinguish foreign or non-self, from self, and initiate their destruction or containment. The sensors or the receptors of the innate immune system accomplish this by recognizing specific molecular patterns, which are common to pathogens or pathogen associated molecules, but absent in the host. We focus on a particular subset of these sensors/receptors, which are involved in sensing virus infection. In order to protect the host from viral invasion, the innate immune system has evolved sensors to detect the viral nucleic acids. Several unique features of virally produced DNA or RNA are exploited to distinguish viral nucleic acids from that of the host. One such unique nucleic acid is double-stranded RNA (dsRNA) – a common byproduct or intermediate in viral genome replication. In mammals, receptors like Toll-like Receptor 3 (TLR3), Retinoic acid-Inducible Gene I (RIG-I) and Melanoma Differentiation-Associated gene-5 (MDA5) are the three known sensors of dsRNA. Single-stranded viral RNA is sensed by Toll-like Receptor 7 and 8 (TLR7 and TLR8), while viral DNA is detected by Toll-like Receptor 9 (TLR9), and other less well characterized receptors. We study four related aspects of innate immunity: (A) the signaling process involved in cytokine production after virus infection, (B) develop modulators for these signaling pathways, (C) how virus evade host innate immune response and (D) the contribution of innate immune response in cancer.   Selected Publications Sen GC, Sarkar SN. The interferon-stimulated genes:targets of direct signalingby interferons, double-stranded RNA, and viruses. Curr Top Microbiol Immunol 2007; 316:233-250.(PMID: 17969451) Sarkar SN, Elco CP, Peters KL et al. Two Tyrosine Residues of Toll-like Receptor 3 trigger Different Steps of NF-{kappa}B Activation. J Biol Chem 2007; 282 (6):3423-3427.(PMID: 17178723) Sen GC, Sarkar SN. Hitching RIG to action. Nat Immunol 2005; 6 (11):1074-1076.(PMID: 16239922) Sen GC, Sarkar SN. Transcriptional signaling by double-stranded RNA: role of TLR3. Cytokine Growth Factor Rev 2005; 16 (1):1-14.(PMID: 15733829) Sarkar SN, Peters GA, Sen GC. Genes Modulated by Interferons and Double-Stranded RNA. In: P Pelese, editor, Modulation of Host Gene Expression and of Innate Immunity by Viruses. London: Kluwer Plenum; 2005; p. 35-65.   Grant Support Title: Novel Modifiers of Toll-like and RIG-like Receptor Signaling. Source: NIH/NIAID Duration: 03/15/2009 − 02/28/2014 Title: Novel Small-Molecule inhibitors of TLR3 – IRF-3 signaling pathway Source: American Heart Association Duration: 01/01/2007 − 12/31/2010   Other Links Sarkar Lab MVP University of Pittsburgh

Saumendra N. Sarkar, Ph.D. Office:  1.8 HCCLB Lab:1.7 HCCLB Phone:(412) 623-7720 saumen@pitt.edu   Academic Affiliations Member Molecular Virology And Microbiology Graduate Program Member Immunology Graduate Program Assistant Professor, Dept. of Microbiology and Molecular Genetics University of Pittsburgh Molecular Virology Program University of Pittsburgh Cancer Institute   Education 1987 BS Presidency College, University of Calcutta, Calcutta, India 1990 MS University College of Science and Technology, University of Calcutta, Calcutta, India 1995 PhD Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India 1996-2008 Post-doc, Research Associate, Project Scientist, Cleveland Clinic   Lab Personnel Jianzhong Zhu, Research Associate Naoki Umemura, Postdoctoral Fellow Adriana Forero, Graduate Student Nelson Hsieh, Undergraduate Student