Sunny
Shin,
Ph.D.
Assistant Professor
Office Address:
Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
201B Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
TEL 215-746-8410
LAB 215-573-4752
FAX 215-898-9557
sunshin@mail.med.upenn.edu
RESEARCH SUMMARY
The focus of our research is to understand how the host tailors appropriate
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 host responses to bacteria that differ in defined virulence properties
and for elucidating mechanisms of bacterial pathogenesis.
We are particularly interested in identifying host 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.
Research projects
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:
Liam Bradley- Graduate Student (MVP)
Alan Copenhaver- Graduate Student (IGG)
Cierra Danko- Graduate Student (MVP)
Thomas Fung - Rotation Student (IGG)
Hieu Nguyen- Research Specialist
Matthew Duda - Undergraduate Student
Derek Jang - Undergraduate Student
Bahar Javdan- Undergraduate Student
Alexandra Vandegrift- Undergraduate Student
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