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Saumendra Sarkar

Saumendra Sarkar

Program: Cancer Virology

saumen@pitt.edu Hillman Cancer Center
Lab 1.7 5117 Centre Avenue
Pittsburgh PA
Summary

Innate immunity of an organism is the inborn protection against invading pathogens. Because it is inborn, and entrusted with the protection of the 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, such as interferons. 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 foreign 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 receptors 7 and 8 (TLR7 and TLR8), while viral DNA is detected by toll-like receptor 9 (TLR9) and other cytoplasmic receptors. We study two related aspects of the signaling process involved in interferon production in the context of infectious disease and cancer: 1) modulation of viral RNA sensing mechanisms; and 2) alternative mechanisms of interferon induction in specific tumors.

Research Interests and Keywords
  • anti-viral innate immunity
  • IFN regulatory factor 3 (IRF3)
  • innate immune signaling
  • interferon (IFN)-stimulated genes
  • RIG-I-like receptors (RLR)
  • toll-like receptor 3 (TLR3)
  • Tumor Microenvironment
  • type I IFN; IFN signaling
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