LABORATORY OF INTRACELLULAR BACTERIA & HOST INTERACTIONS

University of Washington

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Our Research

Mechanisms of Chlamydia Pathogenesis

Our research focus is to solve how the major human pathogen Chlamydia manipulates host cell function in order to cause infectious disease. We apply a diverse array of genetic, cellular, and molecular techniques to reveal the underlying mechanisms of pathogenesis for these highly successful bacteria.

 

Chlamydia exit from host cells

Functional genetics

 

Chlamydia–host proteomics

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The great escape

extrusion strategy of chlamydia exit

Intracellular pathogens have evolved numerous strategies for promoting their exit from host cells, consistent with the essential role of exit for pathogenesis. Yet despite this fundamental importance, microbial exit largely remains an unexplored research area. Efforts in our lab aim to advance understanding of this new theme.

Our pioneering discoveries forged the current understanding of Chlamydia exit from host cells. Chlamydiae possess two mechanisms for accomplishing cellular escape that are mutually exclusive: extrusion and lysis. Extrusion is a packaged release of Chlamydia in which the bacteria are pinched off from the host cell into a membrane-encased compartment, a process that leaves the original host cell intact. Extrusions are novel structures that enhance the biology of Chlamydia infection in many fascinating ways, such as serving as a ‘stealth shuttle’ as these bacteria attempt to elude the host immune system.

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Functional Genetics

Discovery of Chlamydia virulence factors

Genome-wide discovery and characterization of virulence determinants for Chlamydia remains a major unaddressed research area. Through recent landmark advances in genetic manipulation of Chlamydia, and a rich collaboration with Scott Hefty and Dan Rockey, we are working to discover the Chlamydia genes and host protein targets that play critical roles in Chlamydia infection and pathogenesis. 

Chlamydia genome maps

Chlamydiae possess streamlined and highly conserved genomes. These genomes contain valuable information that guides Chlamydia research throughout the world. As part of our ongoing efforts, we maintain annotated genome maps for C. trachomatis D, C. trachomatis L2, and C. muridarum based on current data. 

GET YOUR OWN COPY

Large printed maps (poster size or smaller) can be obtained from Cafepress. This service is great – posters are printed on demand, in varying sizes and formats, and at a very reasonable cost. Alternatively, contact Kevin for digital copies.

Note: I am still putting the final touches on the Cafepress page; let me know if you have any questions or requests.

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Chlamydia–host proteomics

combining genetics & proteomics to illuminate novel chlamydia-host interactions

Successful infection of host cells by Chlamydia requires continuous interactions between scores of bacteria and host proteins, in a manner that ultimately benefits the pathogen. Identification and characterization of these protein interactions is a high priority research area, and may spearhead the development of novel antimicrobials. 

We are developing and exploiting novel proteomic systems to probe unique interactions between intracellular Chlamydia and host cell targets.

 

Featured papers

 

Extrusions are phagocytosed and promote Chlamydia survival within macrophages.
Zuck M, Ellis T, Venida A, Hybiske K
Cell Microbiol (2016)
PubMed | Journal
 

Conservation of extrusion as an exit mechanism for Chlamydia.
Zuck M, Sherrid A, Suchland R, Ellis T, Hybiske K
Pathog Dis (2016)
PubMed | Journal
 

Using fluorescent proteins to visualize and quantitate Chlamydia vacuole growth dynamics in living cells.
Zuck M, Feng C, Hybiske K
J Vis Exp, 104 (2015)
PubMed | Journal


Expanding the molecular toolkit for Chlamydia
Hybiske K
Cell Host & Microbe, 18:11-13 (2015)
PubMed | Journal


Actin recruitment to the Chlamydia inclusion is spatiotemporally regulated by a mechanism that requires host and bacterial factors.
Chin E, Kirker K, Zuck M, James G, Hybiske K
PLoS One, 7:e46949 (2012)
PubMed | Journal


Exit strategies of intracellular pathogens
Hybiske K & Stephens RS
Nature Rev Microbiol, 6:99-110 (2008)
PubMed | Journal


Mechanisms of host cell exit by the intracellular bacterium Chlamydia
Hybiske K & Stephens RS
Proc Natl Acad Sci USA, 104:11430-11435 (2007)
PubMed | Journal


Go to PubMed for a full list of laboratory publications

Current Lab Members

Kevin Hybiske, PhD Assistant Professor Department of Medicine University of Washington  

Kevin Hybiske, PhD
Assistant Professor
Department of Medicine
University of Washington

 

Yibing Wang, PhD Research Scientist

Yibing Wang, PhD
Research Scientist

Meghan Zuck Infectious Diseases & Immunity Graduate Student

Meghan Zuck
Infectious Diseases & Immunity Graduate Student

Mary Dickinson Pathobiology Graduate Student

Mary Dickinson
Pathobiology Graduate Student

Elaina Marie Milton Microbiology Undergraduate

Elaina Marie Milton
Microbiology Undergraduate

Forrest Kwong Cellular and Molecular Biology Undergraduate

Forrest Kwong
Cellular and Molecular Biology Undergraduate

and feat. Bob Suchland Research Scientist

and feat. Bob Suchland
Research Scientist

 

Lab Alumni

Ashley Sherrid, Postdoctoral fellow (University of Washington)
Amy Lee, Undergraduate (University of Washington)
Jessica Cooper, Undergraduate (University of Washington)
Tisha Ellis, Postdoctoral fellow (University of Washington)
Rebecca Peters, Undergraduate (University of Washington)
Erin Bryar, Undergraduate (University of Washington)
Tom Ilustrisimo, Research Associate (UC Berkeley)
Caroline Feng, Research Associate (UC Berkeley)
Desiree Albano, Undergraduate (UC Berkeley)
Elizabeth Chin, Undergraduate (UC Berkeley)
Christina Adams, Undergraduate, UC Berkeley Amgen Scholars Program
Yurika Hara, Undergraduate (UC Berkeley)
Anthony Venida, Undergraduate, UC Berkeley Amgen Scholars Program

The Hybiske Lab is located at the UW Medicine – South Lake Union research cluster, situated near picturesque Lake Union, the Space Needle, the Center for Infectious Disease Research, the Allen Institute, Fred Hutch, and downtown Seattle.

Address

750 Republican Street
Seattle, WA, 98109
United States

 

Contact

khybiske[at]uw.edu
206-616-1549

 

Interested in Joining?

The Hybiske lab is always interested in hearing from innovative individuals: prospective graduate students, postdocs, fellows, and undergraduate students. We are part of an unparalleled nexus of interdepartmental research expertise in microbial pathogenesis, infectious diseases, and global health at the University of Washington. We also engage in collaborative interactions with the Center for Emerging and Reemerging Infectious Diseases (CERID)Global Health, Microbiology, the Center for AIDS and STD, the Center for Infectious Disease Research (CIDR), and the Center for Innate Immunity and Immune Disease (CIIID)

PROSPECTIVE GRADUATE STUDENTS

You must apply (and be accepted by) the Pathobiology PhD Program.

POSTDOCS AND FELLOWS

No current openings available.

UNDERGRADUATE STUDENTS

UW students majoring in Microbiology or similar areas are encouraged to appy. Contact Kevin by email to inquire about possible openings. Please provide a copy of your current academic transcript, a resume, and a detailed statement of why you are a good fit for our possible needs.