Medical Microbiology and Immunology

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Health Science Campus
Health Education Building
Medical Microbiology and Immunology
Room 229, MS1021
Office: 419-383-4323
Fax: 419-383-3002 Microbiology.Immunology@utoledo.edu

Saurabh Chattopadhyay, Ph.D.

Chattopadhyay

Assistant Professor
Virology
Office: HEB 231
Telephone: 419-383-6442
Fax:  419-383-3002
E-mail: Saurabh.Chattopadhyay@utoledo.edu

 

Media Releases:
Read: Article from Jacobson Center for Clinical and Translational Research- How the interferon system controls virus infection

Read:  Article from UT News - Discovery by UT Researcher Reveals a new way the body fights viruses

 

Chattopadhyay laboratory is interested in studying how the interferon system protects against virus infection. In this context, Dr. Chattopadhyay has been studying how a key transcription factor Interferon Regulatory Factor 3 (IRF3) functions to inhibit viral replication in vitro and in vivo. IRF3, upon activation by virus infection, transcriptionally induces many antiviral genes, such as interferons and interferon stimulated genes (ISGs). The protein products of these ISGs inhibit specific stages of viral life cycle, thereby inhibiting virus replication. Because all viruses cannot be inhibited by a single ISG, it is important to investigate virus-specific ISGs. Using high throughput screening approaches, Dr. Chattopadhyay began to identify new viral restriction mechanisms. In future, these mechanisms will be tested in vivo using appropriate viral pathogenesis models.

A major accomplishment of Dr. Chattopadhyay’s research has been the discovery of a new IRF3-dependent antiviral pathway. In this pathway, IRF3 does not require its transcriptional activity, but upon binding with the pro-apoptotic protein BAX, it triggers a direct apoptotic response in the virus-infected cells. Specific protein components are required to trigger this pathway by virus-induced RIG-I activation. This pathway is required for antiviral protection; absence of this pathway leads to viral persistence. Dr. Chattopadhyay’s recent studies illuminated that ubiquitination of IRF3 triggers the apoptotic pathway. Moreover, in the absence of induced antiviral genes, the apoptotic pathway can protect mice against respiratory viral pathogenesis. Using a newly generated knock-in mutant mouse, Dr. Chattopadhyay’s studies demonstrated that IRF3 can provide antiviral protection in the absence of its transcriptional activity. Because the viruses often shut off the host protein synthesis machinery and, therefore, it is critical to provide antiviral defense even in the absence of induced antiviral genes.

Future studies in Dr. Chattopadhyay’s laboratory will involve the finer details of both the transcriptional and apoptotic pathways. Major questions will be how the host selectively uses these pathways in specific cells and protect against viral as well as non-viral diseases.

Dr. Chattopadhyay received his PhD from Indian Institute of Technology Delhi and did his postdoctoral fellowship at Cleveland Clinic under Dr. Ganes Sen. He then worked as a Project Staff and Assistant Professor at Cleveland Clinic Lerner College of Medicine. Dr. Chattopadhyay joined the Department of Medical Microbiology and Immunology in April of 2016.

Current Grant Funding

American Heart Association funded Scientist Development Grant “Innate immune response against respiratory virus infection” (July 2015 – June 2018).


Representative publications

Chattopadhyay S*, Kuzmanovic T, Zhang Y, Wetzel JL and Sen GC*. 2016. Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis. Immunity 44(5): 1151-1161(* Corresponding authors)

Chattopadhyay S, Veleeparambil M, Poddar D, Abdulkhalek S, Bandyopadhyay S, Fensterl V and Sen GC. 2015. EGFR kinase activity is required for TLR4 signaling and the septic shock response. EMBO Reports16(11): 1535-47.

Fensterl V, Chattopadhyay S and Sen GC. 2015. No Love Lost Between Viruses and Interferons. Annual Review of Virology 2: 549-572.

Majumdar T, Chattopadhyay S, Ozhegov E, Dhar J, Goswami R, Sen GC and Barik S. 2015. Induction of interferon-stimulated genes by IRF-3 promotes replication of Toxoplasma gondii. PLoS Pathogens 11(3): e1004779.

Chattopadhyay S and Sen GC. 2014. Meet the Terminator: The Phosphatase PP2A Puts Brakes on IRF-3 Activation. Molecular Cell 54(2): 210-11.

Goswami R, Majumdar T, Dhar J, Chattopadhyay S, Bandyopadhyay S, Verbovetskaya S, Sen GC and Barik S. 2013. Viral degradasome hijacks mitochondria to suppress innate immunity. Cell Research 23(8): 1025-42.

Chattopadhyay S, Fensterl V, Zhang Y, Veleeparambil M, Wetzel JL, and Sen GC. 2013. Inhibition of viral pathogenesis and promotion of the septic shock response to bacterial infection by IRF-3 are regulated by the acetylation and phosphorylation of its coactivators. mBio 4(2): e00636-12.

Chattopadhyay S, Fensterl V, Zhang Y, Veleeparambil M, Yamashita M and Sen GC. 2013. Role of interferon regulatory factor 3-mediated apoptosis in the establishment and maintenance of persistent infection by Sendai virus. Journal of Virology,87(1): 16-24.

Yamashita M, Chattopadhyay S, Fensterl V, Saikia P, Wetzel JL and Sen GC. 2012. Epidermal Growth Factor Receptor is essential for Toll-like Receptor 3 signaling. Science Signaling,5(233): ra50.

Yamashita M, Chattopadhyay S, Fensterl V, Zhang Y and Sen GC. 2012. A TRIF-independent branch of TLR3 signaling. Journal of Immunology,188(6): 2825-2833.

Sears N, Sen GC, Stark GR and Chattopadhyay S.2011. Caspase-8-mediated cleavage inhibits IRF-3 protein by facilitating its proteasome-mediated degradation. Journal of Biological Chemistry, 286(38): 33037-33044.

White CL, Chattopadhyay S and Sen GC. 2011. Phosphatidylinositol 3-kinase signaling delays sendai virus-induced apoptosis by preventing XIAP degradation. Journal of Virology, 85(10): 5224-5227.

Chattopadhyay S, Yamashita M, Zhang Y and Sen GC. 2011. IRF-3/Bax mediated apoptotic pathway, activated by viral cytoplasmic RNA and DNA, inhibits viral replication. Journal of Virology,85(8): 3708-3716.

Chattopadhyay S, Marques JT, Yamashita M, Peters KL, Smith K, Desai A, Williams BR and Sen GC. 2010. Viral apoptosis is induced by IRF-3 mediated activation of Bax. EMBO J29: 1762-1773.

Chattopadhyay S and Sen GC. 2010. IRF-3 and Bax: a deadly affair. Cell Cycle, 9(13) 2479-2480.

Peters KL, Chattopadhyay S and Sen GC. 2008. IRF-3 activation by Sendai virus infection is required for cellular apoptosis and avoidance of persistence. Journal of Virology,82(7): 3500-3508.

 

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Last Updated: 4/20/17