Susan R. Weiss, Ph.D.

faculty photo
Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
203A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076
Office: (215) 898-8013
Fax: (215) 573-4858
Lab: 215-898-3551
Education:
B.A. (Biology)
Brandeis University, 1971.
Ph.D. (Microbiology and Molecular Genetics)
Harvard University, 1975.
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Description of Research Expertise

Research Interests
- Murine coronavirus pathogenesis, central nervous system, liver and lung
- Pathogenesis of human coronaviruses including MERS-CoV, SARS-CoV-2 and other nonlethal human respiratory viruses
- Activation and antagonism of the OAS-RNase L pathway in human and bat cells
- Viral and cellular phosphodiesterases
- Interaction of viruses with dsRNA induced innate immune pathways
- Zika virus pathogenesis
- Endogenous dsRNA induced pathogenesis


Key words: murine coronavirus, SARS-CoV MERS-CoV, human respiratory coronavirus, viral pathogenesis, interferon antagonist, OAS-RNase L.

Description of Research

Susan Weiss, Ph.D.

Professor and vice Chair, Department of Microbiology; Co-Director, Penn Center for Research on Coronaviruses and Other Emerging Pathogens

Office Address:
University of Pennsylvania School of Medicine
203 A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076

TEL 215-898-8013
LAB 215-898-3551
FAX 215-573-4858
weisssr@pennmedicine.upenn.edu


RESEARCH SUMMARY

MOur lab studies murine and human coronavirus pathogenesis, including MHV, MERS-CoV and SARS-CoV. We use MHV infection of mice as a model system for the study of: 1) acute viral encephalitis; 2) chronic demyelinating diseases such as Multiple Sclerosis and 3) virus-induced hepatitis and 4) severe acute respiratory diseases. We have the important tools of a well-developed animal model system and reverse genetic systems with which to manipulate the viral genome. We also investigate pathogenesis of human coronaviruses both the lethal MERS-CoV and SARS-CoV-2 as well as the common cold viruses OC43 and 229E and NL63. We are investigating these both in epithelial cell lines and primary cells and soon in mice. Much of our current work focuses on coronavirus-encoded antagonists of host innate responses. Other foci of the lab are on activation and antagonism of the OAS-RNase L pathway in human and bat cells, the pathogenic effects of endogenous host dsRNA and pathogenesis of Zika virus and other flaviviruses.



ROTATION PROJECT

1. Human coronaviruses. Investigate activation and antagonism of dsRNA induced antiviral pathways during infections with nonlethal human coronaviruses OC43, 229E and NL63. This includes infecting both cell lines and primary respiratory cells with with each of these viruses and assessing actinvion of type I and type III interferon as well as activist of OAS-RNase L and PKR, the data will be compared with ongoing studies on MERS-CoV-2 and SARS-CoV-2. and MHV.

2. Coronavirus EndoU proteins. Investigate the role of EndoU (MHV, MERS-CoV, SARS-CoV-2) in innate immune antagonism. This involves working with wild type and mutant viruses, and comparing both single stranded and double stranded RNA expression using FISH and immunostaining.




Lab personnel:

Yize (Henry) Li- Research Associate
Jillian Whelan- Postdoctoral Researcher
Rebecca Nusbuam- Postdoctoral Researcher
Courtney Comar- Graduate Student
David Renner- Graduate Student
Hanako Reyes - Research Specialist
Nicholas Parenti - Research Specialist
Erick Perez-Jimenez- PENN PREP student

Selected Publications

Li Yize, Banerjee Shuvojit, Goldstein Stephen A, Dong Beihua, Gaughan Christina, Rath Sneha, Donovan Jesse, Korennykh Alexei, Silverman Robert H, Weiss Susan R: Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line. eLife 6, Mar 2017.

Thornbrough Joshua M, Jha Babal K, Yount Boyd, Goldstein Stephen A, Li Yize, Elliott Ruth, Sims Amy C, Baric Ralph S, Silverman Robert H, Weiss Susan R: Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation. mBio 7(2): e00258, Mar 2016.

Li Yize, Banerjee Shuvojit, Wang Yuyan, Goldstein Stephen A, Dong Beihua, Gaughan Christina, Silverman Robert H, Weiss Susan R: Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proceedings of the National Academy of Sciences 113(8): 2241-6, Feb 2016.

Zhao Ling, Jha Babal K, Wu Ashley, Elliott Ruth, Ziebuhr John, Gorbalenya Alexander E, Silverman Robert H, Weiss Susan R: Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology. Cell Host & Microbe 11(6): 607-16, Jun 2012.

Case James Brett, Li Yize, Elliott Ruth, Lu Xiaotao, Graepel Kevin W, Sexton Nicole R, Smith Everett Clinton, Weiss Susan R, Denison Mark R: Murine Hepatitis Virus nsp14 Exoribonuclease Activity Is Required for Resistance to Innate Immunity. Journal of Virology 92(1), 01 2018.

Zhang Rong, Li Yize, Cowley Timothy J, Steinbrenner Adam D, Phillips Judith M, Yount Boyd L, Baric Ralph S, Weiss Susan R: The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine coronavirus JHM.WU. Journal of Virology 89(7): 3598-609, Apr 2015.

Birdwell L Dillon, Zalinger Zachary B, Li Yize, Wright Patrick W, Elliott Ruth, Rose Kristine M, Silverman Robert H, Weiss Susan R: Activation of RNase L by Murine Coronavirus in Myeloid Cells Is Dependent on Basal Oas Gene Expression and Independent of Virus-Induced Interferon. Journal of Virology 90(6): 3160-72, Jan 2016.

Goldstein Stephen A, Thornbrough Joshua M, Zhang Rong, Jha Babal K, Li Yize, Elliott Ruth, Quiroz-Figueroa Katherine, Chen Annie I, Silverman Robert H, Weiss Susan R: Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L. Journal of Virology 91(5), Mar 2017.

Drappier Melissa, Jha Babal Kant, Stone Sasha, Elliott Ruth, Zhang Rong, Vertommen Didier, Weiss Susan R, Silverman Robert H, Michiels Thomas: A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L. PLoS Pathogens 14(4): e1006989, 04 2018.

Zalinger Zachary B, Elliott Ruth, Rose Kristine M, Weiss Susan R: MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus. Journal of Virology 89(24): 12330-40, Dec 2015.

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Last updated: 06/03/2020
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