Saumendra N. Sarkar, PhD

Innate immunity of an organism is the inborn protection against invading pathogens. We are interested in the host innate immune response during virus infection and cancer. Although several basic principles of virus detection and host signaling have been identified, the specific mechanisms by which these pathways are modulated by host components remains poorly understood.

We have been systematically defining regulatory mechanisms during the early and late phase of viral RNA detection and the signaling. We showed that in non-hematopoietic cells in addition to RIG-I activation by viral RNA, additional stimuli, e.g. Ca2+ mobilization, PKC activation are necessary for optimal IFN induction and protection against virus replication (Zhu et al, 2011). However, following initial induction of IFN, a number of IFN-stimulated genes (ISG) are induced, which again profoundly modulate the RLR signaling pathway – the so called late modulators. One such protein Oligoadenylate synthetase-like (OASL) increases the sensitivity of RIG-I signaling by mimicking one of the RIG-I-ligand, and exerts a strong antiviral activity against multiple RNA viruses (Zhu et al, 2014) Yet another protein, MOV10 (Moloney leukemia virus 10 homolog) seemed to be involved in initiating another parallel signaling process when stimulated by viral RNA (Cuevas et al, 2014). Therefore, these modulators together control and fine tune the antiviral innate immune response, which can be targeted for future development of novel therapies against specific viral diseases.

Another major interest of my lab is to define the role of innate immune responses, specifically IFN response in shaping tumorigenesis and metastasis. Using viral oncoprotein expression, we found that the DNA-damage response induced in many tumor cells due to their high replication stress may be responsible for this IFN induction in the TME (Forero et al, 2014). Another recently discovered IFN induction pathway mediated by DNA-sensor signaling also contributes to this process (Ohkuri et al, 2014). Currently, we are focused on understanding these signaling processes that are involved in inducing IFN in the TME.

Sarkar Lab Website

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