Medical Microbiology and Immunology

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

OPEN POSITIONS IN THE LAB OF DR. CHATTOPADHYAY
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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; the 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 2019).
National Institutes of Health funded R21 Grant “How non-transcriptional IRF3 prevents ALD” (Sep 2018 – Aug 2020).
University of Toledo Medical Research Society funded Grant “Novel therapeutics against respiratory virus infection” (July 2019 – June 2020).

Chattopadhyay Lab Group
Research Group
Back row (L to R): Grace Steimle (undergraduate student), Saurabh Chattopadhyay, Merina Varghese (undergraduate student), Karan Chawla (MD student), and Anna Glanz (MS student)
Front row (L to R): Sukanya Chakravarty (PhD student), Tia Rahman (MD student), Gayatri Subramanian (PhD student), and Sonam Popli (Postdoc)


Representative publications

NCBI My Bibliography

Glanz A, Chawla K, Fabry S, Subramanian, G, Garcia, J, Jay, B, Ciricillo, J, Chakravarti, R, Taylor, R.T., Chattopadhyay, S. 2020. High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication. Viruses. 2020;12(4):E442. Published 2020 Apr 14. doi:10.3390/v12040442

Subramanian G, Popli S, Chakravarty S, Taylor RT, Chakravarti R, Chattopadhyay S.
2020. The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication [published online ahead of print, 2020 Apr 9]. J Biol Chem. 2020;jbc.RA120.013533. doi:10.1074/jbc.RA120.013533

Sanz-Garcia C, McMullen MR, Chattopadhyay S, Roychowdhury S, Sen G, Nagy LE.
2019. Nontranscriptional Activity of Interferon Regulatory Factor 3 Protects Mice From High-Fat Diet-Induced Liver Injury. Hepatol Commun. 2019;3(12):1626–1641. Published 2019 Oct 10. doi:10.1002/hep4.1441


McGowan J, Peter C, Chattopadhyay S, Chakravarti R.
2019. 14-3-3ζ-A Novel Immunogen Promotes Inflammatory Cytokine Production. Front Immunol. 2019;10:1553. Published 2019 Jul 24. doi:10.3389/fimmu.2019.01553

Youseff BH, Brewer TG, McNally KL, Izuogou, AO, Lubick, KJ, Presloid, JB, Alqahtani, A, Chattopadhyay, S, Best, SM, Hu, Xiche, Taylor, RT. 2019. TRAF6 Plays a Proviral Role in Tick-Borne Flavivirus Infection through Interaction with the NS3 Protease. iScience. 2019;15:489–501. doi:10.1016/j.isci.2019.05.010

Sanz-Garcia C, Poulsen KL, Bellos D, Wang, H, McMullen, MR, Li, X, Chattopadhyay, S, Sen, G, Nagy, L. 2019. The non-transcriptional activity of IRF3 modulates hepatic immune cell populations in acute-on-chronic ethanol administration in mice. J Hepatol. 2019;70(5):974–984. doi:10.1016/j.jhep.2019.01.021

Subramanian G, Kuzmanovic T, Zhang Y, Peter CB, Veleeparambil M, Chakravarti R, Sen GC and Chattopadhyay S. 2018.
A new mechanism of interferon's antiviral action: induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7. PLOS Pathogens 14(1): e1006877.

Subramanian G, Chakravarti R, Chattopadhyay S. 2018. Ifi204/p204, a new piece in the sepsis puzzle. Ann Transl Med. 2018;6(Suppl 1):S12. doi:10.21037/atm.2018.09.22

McGowan JE, Kratch J, Chattopadhyay S, Joe B, Conti HR, Chakravarti R. 2017. Bioinformatic analysis reveals new determinants of antigenic 14-3-3 proteins and a novel antifungal strategy. PLOS One 12(12): e0189503.

Veleeparambil M, Poddar D, Abdulkhalek S, Kessler PM, Yamashita M, Chattopadhyay S and Sen GC. 2018. Constitutively bound EGFR-mediated tyrosine phosphorylation of TLR9 is required for its ability to signal. Journal of Immunology 200(8): 2809-1818.

Chattopadhyay S* and Sen GC*. 2017. RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway. Protein & Cell 8(3): 165-68. (*Corresponding authors)

Wang X, Majumdar T, Kessler P, Ozhegov E, Zhang Y, Chattopadhyay S, Barik S and Sen GC. 2016. STING requires the adaptor TRIF to trigger innate immune responses to microbial infection. Cell Host Microbe 20(3): 329-41.

Chattopadhyay S*, Kuzmanovic T, Zhang Y, Wetzel JL and Sen GC*. 2016. Ubiquitination of IRF-3 activates RIPA, the apoptotic pathway that protects mice from viral pathogenesis. Immunity44(5) 1151-61. (* 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 Cell54(2): 210-11.

Goswami R, Majumdar T, Dhar J, Chattopadhyay S, Bandyopadhyay S, Verbovetskaya S, Sen GC and Barik S. 2013. An RNA 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 bacterial septic shock response by IRF-3 are regulated by acetylation and phosphorylation of its co-activators. mBio 4(2): e00636-12.

Chattopadhyay S, Fensterl V, Zhang Y, Veleeparambil M, Yamashita M and Sen GC. 2013. Role of IRF-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 Signaling5(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 by facilitating its proteasome-mediated degradation. Journal of Biological Chemistry286(38): 33037-33044.

White CL, Chattopadhyay S and Sen GC. 2011. PI3K 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 Virology85(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 J 29: 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 Virology82(7): 3500-3508.

 

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Last Updated: 8/31/20