Department of Microbiology

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Faculty Profile

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Sunny Shin, Ph.D.

Assistant Professor of Microbiology
Member, Institute for Immunology, University of Pennsylvania Perelman School of Medicine
Department: Microbiology

Contact information
3610 Hamilton Walk
201B Johnson Pavilion
Philadelphia, PA 19104
Office: (215) 746-8410
Fax: (215) 898-9557
Lab: (215) 573-4752
Graduate Group Affiliations
Education:
B.S. (Biology)
Massachusetts Institute of Technology, 1998.
Ph.D. (Microbiology & Immunology)
Stanford University School of Medicine, 2004.
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Description of Research Expertise

The focus of our research is to understand how the host tailors appropriate innate immune responses to different classes of bacteria and how intracellular pathogens are able to subvert host defenses. We utilize the intracellular pathogen Legionella pneumophila as a model to address these questions. Legionella causes a severe pneumonia known as Legionnaires’ disease in humans. Essential for Legionella‘s virulence is a specialized type IV secretion system that delivers effector proteins into the host cytosol. These bacterial effectors modulate multiple eukaryotic cellular processes, thus enabling Legionella to survive and replicate inside host cells. The ease with which Legionella can be manipulated genetically facilitates the comparison of wild-type and mutant bacteria. Thus, Legionella provides a powerful model system for dissecting immune responses to bacteria that differ in defined virulence properties and for elucidating mechanisms of bacterial pathogenesis.

We are particularly interested in identifying host immune pathways that respond to bacterial type IV secretion systems and virulence activities. Using various bacterial mutants and mouse strains with select immune deficiencies, we have found that the immune system distinguishes between virulent and avirulent bacteria and mounts a sustained proinflammatory immune response only to virulent bacteria. This response to virulent Legionella requires coincident immune detection of bacterial structures as well as cytosolic detection of the type IV secretion system and other virulence determinants. We believe that further identification of host pathways altered during Legionella infection will allow us to identify additional immune sensing pathways as well as bacterial virulence strategies involved in manipulating host cell processes. We are examining how these various host pathways collaborate to generate antibacterial immunity in vivo. We are also extending our studies to other intracellular bacterial pathogens in order to identify shared and unique features of immune detection and bacterial virulence. Insight into these areas will advance our understanding of bacterial pathogenesis, how the innate immune system distinguishes between virulent and avirulent bacteria and initiates antimicrobial immunity, and will ultimately aid in the design of effective antimicrobial therapies and vaccines.

Students are encouraged to contact Dr. Shin about potential rotation projects. Depending on the student's research interests, there are projects in the following areas:

1. Host signaling pathways altered during bacterial infection.
2. Regulation of immune gene expression during bacterial infection.
3. In vivo immune responses to bacterial infection.

Lab personnel:
Cierra Danko- Graduate Student (MVP)
Liam Bradley- Graduate Student (MVP)
Alan Copenhaver- Graduate Student (IGG)
Janet Yu- Research Specialist
Matthew Duda- Undergraduate Student
Ingharan Siddarthan- Undergraduate Student

Selected Publications

Copenhaver, A.M., Casson, C.N., Nguyen, H.T., Fung, T.C., Duda, M.M., Roy, C.R., Shin, S. : Alveolar macrophages and neutrophils are the primary reservoir for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion. Infection & Immunity pii(IAI.01891-14), Aug 2014.

Philip, N.H., Dillon, C.P., Snyder, A.G., Fitzgerald, P., Wynosky-Dolfi, M.A., Zwack, E.E., Hu, B., Fitzgerald, L., Mauldin, E.A., Copenhaver, A.M., Shin, S., Wei, L., Parker, M., Zhang, J., Oberst, A., Green, D.R., & Brodsky, I. : Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling. Proceedings of the National Academy of Sciences 111(20): 7385-90, May 2014.

Casson, C.N., Copenhaver, A.M., Zwack, E.E., Nguyen, H.T., Strowig, T., Javdan, B., Bradley, W.P., Fung, T.C., Flavell, R.A., Brodsky, I.E., & Shin, S.: Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLOS Pathogens 9(6): e1003400, 2013.

Fontana, M.F., Shin, S., & Vance, R.E.: Activation of host mitogen-activated protein kinases by secreted Legionella pneumophila effectors that inhibit host protein translation. Infection and Immunity 80(10): 3570-5, 2012.

Lippman J, Müller HC, Naujoks J, Tabeling C, Shin S, Witzenrath M, Hellwig K, Kirschning CJ, Taylor GA, Barchet W, Bauer S, Suttorp N, Roy CR, Opitz B. : Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice. Cellular Microbiology 13(11): 1668-1682, 2011.

Jensen, K.D.C.*, S. Shin*, and Y-h Chien : Cutting edge: intraepithelial lymphocytes of the small intestine are not biased toward thymic antigens Journal of Immunology 182(12): 7348 - 7351, 2009 Notes: *equal contribution.

Nogueira, C.V., T. Lindsten, A.M. Jamieson, C.L. Case, S.Shin, C.B. Thompson, and C.R. Roy: Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila. PLoS Pathogens 5(6), 2009.

Case, C.L., S. Shin, and C.R. Roy: Asc and Ipaf inflammasomes direct distinct pathways for caspase-1 activation in response to Legionella pneumophila. Infection and Immunity 77(5): 1981 - 1991, 2009.

Shin, S., C.L. Case, K.A. Archer, C.V. Nogueira, K.S., Kobayashi, R.A. Flavell, C.R. Roy, and D.S. Zamboni: Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila. PLoS Pathogens 4(11), 2008.

Jensen, K.D.C., X. Su, S.Shin, L.Li, S. Youssef, S. Yamasaki, L. Steinman, T. Saito, R.M. Locksley, M.M. Davis, N. Baumgarth, and Y-h Chien: Thymic selection determines gd T cell effector fate: Antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon-gamma. Immunity 29: 90 - 100, 2008.

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Last updated: 10/24/2014
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