Sunny Shin

faculty photo
Assistant Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

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

My lab is interested in uncovering molecular and cellular mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade or manipulate host defenses.

We utilize the intracellular bacterial pathogen Legionella pneumophila, causative agent of the severe pneumonia Legionnaires' disease, as a model. Legionella has evolved numerous mechanisms to modulate eukaryotic processes in order to facilitate its survival and replication inside host cells. The ease with which Legionella can be genetically manipulated provides a powerful model system for dissecting immune responses to bacteria that differ in defined virulence properties and for elucidating mechanisms of bacterial pathogenesis.

A major focus of our lab has involved the identification of innate immune pathways that enable the immune system to distinguish between virulent and avirulent bacteria and specifically mount robust proinflammatory responses against virulent bacteria. One of these key immune pathways involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1 and caspase-11 in response to bacterial products introduced into the host cell cytosol. These caspases mediate the release of IL-1 family cytokines and other inflammatory responses critical for host defense, but overexuberant activation leads to pathological outcomes such as septic shock. We are currently pursuing how inflammasomes are differentially regulated in mice and humans in response to bacterial infection, as mice and humans differ in several key inflammasome components.

We are also uncovering how the immune system successfully overcomes the ability of pathogens to suppress host functions critical for immune defense. We recently found that infected macrophages circumvent the ability of Legionella to block host translation by synthesizing and releasing key cytokines that instruct bystander uninfected cells to generate an effective immune response. We are defining additional mechanisms that mediate communication between infected and bystander cells and eventual control of bacterial infection. We also examine immune responses to other bacterial pathogens with the goal of identifying shared and unique features of innate immunity 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.

Prospective students and postdocs are encouraged to contact Dr. Shin. Depending on the person's research interests, there are projects in several different areas.

Lab personnel:
Liam Bradley- Graduate Student
Valeria Reyes Ruiz- Graduate Student
Cierra Casson- Postdoc
Alicia Holmgren- Postdoc
Mark Boyer- Research Specialist
Jasmine Ramirez- Research Specialist
Sylvia Guan- Undergraduate Student
Helen Fetaw- Undergraduate Student
Ingharan Siddarthan- Undergraduate Student
Brian Yan- Undergraduate Student

Selected Publications

Copenhaver, A.M., Casson, C.N., Nguyen, H.T., Duda, M.M., and Shin, S.: IL-1R signaling enables bystander cells to overcome bacterial blockade of host protein synthesis. Proceedings of the National Academy of Sciences 112(24): 7557-62, 2015.

Casson, C.N., Yu, J., Reyes, V.M., Taschuk, F.O., Yadav, A., Copenhaver, A.M., Nguyen, H.T., Collman, R.G., and Shin, S.: Human caspase-4 mediates non-canonical inflammasome activation against Gram-negative bacterial pathogens. Proceedings of the National Academy of Sciences 112(21): 6683-93, 2015.

Shin, S. and Brodsky, I.E.: The inflammasome: Learning from bacterial evasion strategies. Seminars in Immunology pii: : S1044-5323(15)00014-7, 2015.

Copenhaver, A.M., Casson, C.N., Nguyen, H.T., Fung, T.C., Duda, M.M., Roy, C.R., and Shin, S. : Alveolar macrophages and neutrophils are the primary reservoir for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion. Infection and Immunity 82(10): 4325-36, 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., and 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, 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., and Shin, S.: Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLOS Pathogens 9(6): e1003400, 2013.

Casson, C.N. and Shin, S. : Inflammasome-mediated cell death in response to bacterial pathogens that access the host cytosol: lessons from Legionella pneumophila. Frontiers in Cellular and Infection Microbiology 3: 111, 2013.

Fontana, M.F., Shin, S., and 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.

Shin, S.: Innate immunity to intracellular pathogens: Lessons learned from Legionella pneumophila. Advances in Applied Microbiology. Elsevier, 79: 43-71, 2012.

Lippman, J., Müller, H.C., Naujoks, J., Tabeling, C., Shin, S., Witzenrath, M., Hellwig, K., Kirschning, C.J., Taylor, G.A., Barchet, W., Bauer, S., Suttorp, N., Roy, C.R., and Opitz, B. : Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice. Cellular Microbiology 13(11): 1668-82, 2011.

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Last updated: 08/12/2015
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