Sunny Shin, Ph.D.

faculty photo
Associate Professor of Microbiology
Member, Institute for Immunology, University of Pennsylvania Perelman School of Medicine
Core Leadership Council Member, Penn Center for Genome Integrity, University of Pennsylvania Perelman School of Medicine
Program Leader, Innate and Adaptive Immunity to Pathogens, Institute for Immunology
Vice-Chair of Diversity and Inclusion, Department of Microbiology, University of Pennsylvania Perelman School of Medicine
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.
Cert. (Unconscious Bias Training: Impact on Decision Making)
University of Pennsylvania Perelman School of Medicine, 2020.
Cert. (Inclusive and Equitable Teaching Seminar)
Center for Teaching and Learning, University of Pennsylvania, 2021.
Cert. (HHMI Gilliam Mentorship Training)
HHMI and CIMER, 2022.
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Description of Research Expertise

My lab is interested in uncovering innate immune mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade host immunity to cause disease.

We utilize the intracellular bacterial pathogen Legionella pneumophila, causative agent of the severe pneumonia Legionnaires' disease, as our primary model. Legionella has evolved numerous mechanisms for modulating eukaryotic processes in order to survive and replicate within host cells. The ease with which Legionella can be genetically manipulated provides a powerful 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 is to understand how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses. One key immune pathway involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1 and caspase-11 upon cytosolic detection of bacterial products. These caspases mediate the release of IL-1 family cytokines and other inflammatory factors critical for host defense, but overexuberant activation can lead to pathological outcomes such as septic shock. We are currently pursuing how mouse and human inflammasomes differentially respond to bacterial infection.

We are also interested in elucidating how the immune system successfully overcomes the ability of pathogens to suppress critical immune functions. We recently found that infected macrophages circumvent Legionella's ability to block host translation by selectively synthesizing and releasing key cytokines. These cytokines then instruct bystander immune cells to generate an effective immune response. We are defining additional mechanisms that facilitate communication between infected and bystander cells and promote antimicrobial defense.

We also study the evolutionarily related pathogen Coxiella burnetii, and other bacterial pathogens, including Salmonella Typhimurium and Yersinia spp., 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 to learn more about our research.

Lab personnel:
Xin Liu, Ph.D.- Postdoctoral Fellow (K99 award)
Marisa Egan- Graduate Student (CAMB-MVP; NSF fellowship)
Mikel Haggadone, Ph.D.- Postdoctoral Fellow
Neha Nataraj- Graduate Student (IGG; T32 training grant; co-mentored with Igor Brodsky)
Emily O'Rourke- Graduate Student (CAMB-MVP; CAMB T32 training grant)
Stephanie Schreiner- Graduate Student (IGG; NSF fellowship)
Jaydeen Sewell- Graduate Student (CAMB-MVP)
Victor Vazquez Marrero- Graduate Student (IGG; NSF fellowship)
Kimberly Wodzanowki, Ph.D.- PennPORT Postdoctoral Fellow
Ling Wu, M.D., Ph.D.- Pulmonary and Critical Care Fellow
Jenna Zhang- Graduate Student (CAMB-MVP MSTP; co-mentored with Igor Brodsky)
Mark Boyer, M.S.- Research Specialist C
Tabitha Demissie- Undergraduate Student
Klarissa Diaz- Undergraduate Student
Allyson Lu- Undergraduate Student

Selected Publications

Naseer, N.*, Egan, M.*, Reyes Ruiz, V.M.*, Scott, W.P., Hunter, E.N., Demissie, T., Rauch, I., Brodsky, I.E., Shin, S.: Human NAIP/NLRC4 and NLRP3 inflammasomes detect Salmonella type III secretion system activities to restrict intracellular bacterial replication. PLOS Pathogens 18(1): e1009718, 2022.

Alexander-Floyd, J.^, Bass, A.R.^, Harberts, E.M.^, Grubaugh, D., Buxbaum, J.D., Brodsky, I.E., Ernst, R.K.*, Shin, S.* : Lipid A variants activate human TLR4 and the noncanonical inflammasome differently and require the core oligosaccharide for inflammasome activation. Infection and Immunity 90(8): e0020822, 2022 Notes: ^co-first authors; *co-corresponding authors.

Naseer, N., Zhang, J., Bauer, R., Constant, D.A., Nice, T.J., Brodsky, I.E., Rauch, I.*, Shin, S.*: Salmonella enterica Serovar Typhimurium Induces NAIP/NLRC4- and NLRP3/ASC-Independent, Caspase-4-Dependent Inflammasome Activation in Human Intestinal Epithelial Cells. Infection and Immunity 90(7): e0066321, 2022 Notes: *co-corresponding authors; selected for Infection and Immunity Editor's Spotlight.

Lopes Fischer, N., Boyer, M.A., Bradley, W.P., Spruce, L.A., Fazelinia, H., Shin, S.: A Coxiella burnetii effector interacts with the host PAF1 complex and suppresses the innate immune response. bioRxiv DOI: 10.1101/2022.04.20.488957, 2022.

Pollock, T.Y., Vázquez Marrero, V.R., Brodsky, I.E., Shin, S.: TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection. bioRxiv DOI: 10.1101/2022.07.29.501970, 2022.

Liu, X., Boyer, M.A., Holmgren, A.M., & Shin, S.: Infected macrophages engage alveolar epithelium to metabolically reprogram myeloid cells and promote antibacterial inflammation. Cell Host & Microbe 28(5): 683-698, 2020.

Bass, A.R. & Shin, S.: Human GBP1 promotes pathogen vacuole rupture and inflammasome activation during Legionella pneumophila infection. bioRxiv Page: https://doi.org/10.1101/2020.05.27.120477, 2020.

Lopes Fischer, N.L.*, Naseer, N.*, Shin, S.#, and Brodsky, I.E.#: Effector-triggered immunity and pathogen sensing in metazoans. Nature Microbiology 5(1): 14-26, 2020 Notes: *equal contribution, listed in alphabetical order; #co-corresponding author.

Reyes Ruiz, V.M., Ramirez, J., Naseer, N., Palacio, N.M., Siddarthan, I.J., Yan, B.M., Boyer, M.A., Pensinger, D.A., Sauer, J-D., and Shin, S.: Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome. Proceedings of the National Academy of Sciences 114(50): 13242-13247, 2017.

Casson, C.N.*, Doerner, J.L.*, Copenhaver, A.M., Ramirez, J., Holmgren, A.M., Boyer, M.A., Siddarthan, I.J., Rouhanifard, S.H., Raj, A., and Shin, S.: Neutrophils and Ly6Chi monocytes collaborate in generating an optimal cytokine response that protects against pulmonary Legionella pneumophila infection. PLOS Pathogens 13(4): e1006309, 2017 Notes: *co-first authors; listed in alphabetical order.

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Last updated: 11/30/2022
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