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Saumendra N. Sarkar, PhD



Dr. Saumen Sarkar

Contact

412-623-7720
Fax: 412-623-7715
1.8 Hillman Cancer Center
5117 Center Avenue

Education

PhD in Molecular Biophysics, Indian Institute of Science, Bangalore (India)

MS in Biophysics & Molecular Biology, University College of Science and Technology, University of Calcutta (India)

BS in Physiology, Physics and Chemistry, Presidency College, University of Calcutta (India)


Academic Affiliation(s)

Associate Professor, Department of Microbiology and Molecular Genetics

Associate Professor, Department of Immunology

Member, Cancer Virology Program, University of Pittsburgh Cancer Institute

Member, Molecular Virology and Microbiology Graduate Program

Member, Immunology Graduate Program

Research

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.

Lab Personnel

Arundhati Ghosh, Ph.D. Research Scientist
Jianzhong Zhu, Ph.D. Research Associate
Adriana Forero, Graduate Student
Kevin McCormick, Graduate Student
Rolando Cuevas, Research Specialist

Areas of Interest

Innate Immunity; Virus; Interferon; Signaling; Cancer

Publications

Umemura N, Zhu J, Mburu Y. K, Forero A, Hsieh P. N, Muthuswamy R, Kalinski P, Ferris R. L, and Sarkar S. N. Defective NF-kappaB signaling in metastatic head and neck cancer cells leads to enhanced apoptosis by double-stranded RNA. Cancer Res. 72: 45-55. |  View Abstract

Kohanbash G, Ishikawa E, Fujita M, Ikeura M, McKaveney K, Zhu J, Sakaki M, Sarkar S. N, and Okada H. Differential activity of interferon-alpha8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma. Oncoimmunology. 1: 487-492. |  View Abstract

Bozym R. A, Delorme-Axford E, Harris K, Morosky S, Ikizler M, Dermody T. S, Sarkar S. N, and Coyne C. B. Focal adhesion kinase is a component of RIG-I-like receptor antiviral signaling. Cell Host Microbe. 11: 153-166. |  View Abstract

Zhu J, Coyne C. B, and Sarkar S. N. PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and beta-catenin. Embo J. 30: 4838-4849. |  View Abstract

Morosky S. A, Zhu J, Mukherjee A, Sarkar S. N, and Coyne C. B. Retinoic acid-induced gene-I (RIG-I) associates with nucleotide-binding oligomerization domain-2 (NOD2) to negatively regulate inflammatory signaling. J Biol Chem. 286: 24574-28583. |  View Abstract

Mburu Y. K, Abe K, Ferris L. K, Sarkar S. N, Ferris R. L. Human beta-defensin 3 promotes NF-kappaB-mediated CCR7 expression and anti-apoptotic signals in squamous cell carcinoma of the head and neck. Carcinogenesis. 32: 168-174. |  View Abstract

Zhu J, Smith K, Hsieh P. N, Mburu Y. K, Chattopadhyay S, Sen G. C, and Sarkar S. N. High-throughput screening for TLR3-IFN regulatory factor 3 signaling pathway modulators identifies several antipsychotic drugs as TLR inhibitors. J Immunol. 184: 5768-5776. |  View Abstract