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: Discussed the NIH grant award and the science with the NBC News network
Read: Discussed the NIH grant award with The Blade, Toledo newspaper
Read: UT News article on NIH grant award
Read: Dean’s update on NIH grant award
Read: Article from WTOL – COVID-19 surveillance in wastewater
Read: Article from WTOL - Ohio Hepatitis A Outbreak in Lucas County
Read: 
UT News Article - UT Researcher Reveals a new way the body fights viruses
Read: JCCTR article - how the interferon system controls virus infection

OPEN POSITIONS IN THE LAB OF DR. CHATTOPADHYAY
Lab Research Tech: Click For More Information
Post-doctoral Position: Click for More Information

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 the viral life cycle, thereby inhibiting virus replication. Because a single ISG cannot inhibit all viruses, it is important to investigate virus-specific ISGs. Using high throughput screening approaches, Dr. Chattopadhyay began to identify new viral restriction mechanisms. In the 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 non-transcriptional pathway of IRF3 to kill the virus-infected cells. IRF3 does not require its transcriptional activity in this pathway, 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 newly-generated knock-in mice, Dr. Chattopadhyay’s studies demonstrated that the apoptotic function of IRF3 provides antiviral protection in the absence of its transcriptional activity. Because the viruses often shut off the host protein synthesis machinery, it is critical to provide antiviral defense even in the absence of induced antiviral genes.

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

Dr. Chattopadhyay received his PhD from the 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.

Grant Funding:

NIH/NIAID RO1 Grant “Anti-inflammatory functions for non-transcriptional IRF3” (Feb 2021 – Jan 2026). Role: Principal Investigator.

NIH/NIAID RO1 Grant “Understanding the pro-viral role for TRAF6 interaction with the viral protease in flavivirus replication and pathogenesis” (July 2020 – June 2025). Role: Co-Investigator (PI: Travis Taylor, University of Toledo).

NIH/NIAAA-funded RO1 Grant “Transcriptional and non-transcriptional functions of IRF3 in ALD” (July 2019 – June 2022). Role: Co-Investigator (PI: Laura Nagy, Cleveland Clinic).

 NIH/NIAID R21 grant “A novel model to study COVID-19 and Hypertension” (July 2021 – June 2023). Role: Co-Investigator (PI: Bina Joe, University of Toledo).

CDC/EPA/ODH grant “State of Ohio Wastewater SARS-CoV-2 Surveillance Project” (July 2020 – June 2022). Role: Co-Investigator (PI: Zuzana Bohrerova, Ohio State University).

Medical Research Society grant “Antiviral drugs against respiratory virus infection” (July 2019 – June 2022). Role: Principal Investigator.

American Heart Association (AHA) funded Scientist Development Grant “Innate immune response against respiratory virus infection” (July 2015 – June 2019). Role: Principal Investigator.

NIH/NIAAA-funded R21 Grant “How non-transcriptional IRF3 prevents ALD” (Sep 2018 – Aug 2021). Role: Principal Investigator.


Chattopadhyay Lab Group
Research Group

Back row (L to R): Vikash Kumar (Research Associate), Saurabh Chattopadhyay, Johnathon Durgala (Research Technician), Shreyas Gujja (MSBS student)

Front Row (L to R): Merina Varghese (undergraduate student), Shumin Fan (MD/PhD student), Sukanya Chakravarty (PhD Student), Quinn Carter (High School student)


Representative Publications:

NCBI My Bibliography

Glanz A, Chakravarty S, Varghese M, Kottapalli A, Fan S, Chakravarti R, and Chattopadhyay S. 2021. Transcriptional and non-transcriptional activation, posttranslational modifications, and antiviral functions of Interferon Regulatory Factor 3 and viral antagonism by the SARS-coronavirus. Viruses 13(4): 575.

 Kim J, Chun, K, McGowan JE, Zhang Y, Czernik PJ, Mell B, Joe B, Chattopadhyay S, Holoshitz J and Chakravarti R. 2021. 14-3-3z: A novel suppressor of inflammatory arthritis. Proc Natl Acad Sci, USA118(34):e2025257118.

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 12(4): E442.

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. J Biol Chem, 295(20): 6811-6822.

 McGowan JE, Peter C, Kim J, Popli S, Veerman B, Saul-McBeth J, Conti H, Pruett-Miller, SM, Chattopadhyay S, and Chakravarti R. 2020. 14-3-3z-TRAF5 Axis Governs Interleukin-17A Signaling. Proc Natl Acad Sci, USA 117(40): 25008-25017.
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 Comm 3(12):1626–1641.

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 15:489–501.

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 Hepatol70(5):974–984.

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.

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. Immunity 44(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 Rep16(11): 1535-47.

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

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. mBio4(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. J Virol87(1): 16-24.

Sears N, Sen GC, Stark GR and Chattopadhyay S.2011. Caspase-8 mediated cleavage inhibits IRF-3 by facilitating its proteasome-mediated degradation. J Biol Chem286(38): 33037-33044.

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. J Virol85(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.


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Last Updated: 9/8/21