Susan R. Weiss, Ph.D.

faculty photo
Professor of Microbiology
Vice Chair, Departmet of Microbiology, University of Pennsylvania
Co-Director, Penn Center for Research on Coronaviruses and Other Emerging Pathogens, University of Pennsylvania
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

Our 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 in primary human nasal epitheli culutres gwon on air liquid interface. 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 activation 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.

3. Human coroanvirus infections of primary nasal cells




Lab personnel:

Nikki Tannetti- Postdoctoral Researcher
Nicole Bracci-Postdoctoral Researcher
David M Renner- Graduate Student
Clayton Otter- Graduate Student (combined MD, PhD)
Alejandra Fausto -Graduate Student
Helen Stillwell- Graduate Student
Ellie Sell- Medical/MTR Student
Nicholas A Parenti - Research Specialist
Anant Patel- Research Specialist

Selected Publications

Otter CJ, Fausto A, Tan LH, Khosla AS, Cohen NA, Weiss SR.: Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses. Proc Natl Acad Sci U S A 120: e2218083120, Apr 2023.

Comar CE, Otter CJ, Pfannenstiel J, Doerger E, Renner DM, Tan LH, Perlman S, Cohen NA, Fehr AR, Weiss SR.: MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells. Proc Natl Acad Sci U S A 119: e2123208119, May 2022.

Nguyen LC, Renner DM, Silva D, Yang D, Parenti NA, Medina KM, Nicolaescu V, Gula H, Drayman N, Valdespino A, Mohamed A, Dann C, Wannemo K, Robinson-Mailman L, Gonzalez A, Stock L, Cao M, Qiao Z, Moellering RE, Tay S, Randall G, Beers MF, Rosner MR, Oakes SA, Weiss SR.: SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells. mBio 13: e0241522, Oct 2022.

Li Y, Renner DM, Comar CE, Whelan JN, Reyes HM, Cardenas-Diaz FL, Truitt R, Tan LH, Dong B, Alysandratos KD, Huang J, Palmer JN, Adappa ND, Kohanski MA, Kotton DN, Silverman RH, Yang W, Morrisey EE, Cohen NA, Weiss SR.: SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes. Proc Natl Acad Sci U S A 118: e2022643118, Apr 2021.

Weiss SR.: Forty years with coronaviruses. J Exp Med 217: e20200537, May 2020.

Ancar R, Li Y, Kindler E, Cooper DA, Ransom M, Thiel V, Weiss SR, Hesselberth JR, Barton DJ.: Physiologic RNA targets and refined sequence specificity of coronavirus EndoU. RNA 26: 1976-1999, Dec 2020.

Comar CE, Goldstein SA, Li Y, Yount B, Baric RS, Weiss SR.: Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection. mBio 10: e00319-19, Mar 2019.

Li Y, Dong B, Wei Z, Silverman RH, Weiss SR.: Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling. mBio 10: e02414-19, Nov 2019.

Thornbrough JM, Jha BK, Yount B, Goldstein SA, Li Y, Elliott R, Sims AC, Baric RS, Silverman RH, Weiss SR.: Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation. mBio 7: e00258, Mar 2016.

Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J, Gorbalenya AE, Silverman RH, Weiss SR.: 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: 607-16, Jun 2012.

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Last updated: 10/17/2023
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