David Koelle,  M.D.
Professor of Medicine

CONTACT INFORMATION
1616  Eastlake Ave E, Suite 500
Seattle, WA 98102

UW Mail stop 358117
Seattle, WA 98195-8117

Phone: (206) 667-6491
Fax: (206) 206-667-7711
viralimm@u.washington.edu

LINK TO DAVID KOELLE'S COMMUNITY OF SCIENCE WEB PAGE

CURRENT RESEARCH INTERESTS

The Koelle Lab studies host innate and acquired cellular immune responses to infections, pathogen genetic variation, and the relationship between host genomics and infection severity.  Pathogens of interest include herpes simplex viruses types 1 and 2, vaccinia (the vaccine agent for smallpox), and P. falciparum.  These agents all have large genomes, so determination of the antigens that drive T-cell responses is a non-trivial problem.  Our specific technical expertise is in the use of genomic libraries and genome-spanning ORF sets, which we combine with artificial or defined antigen presenting cells to interrogate CD8 and CD4 T-cell responses to a high level of definition.  In addition to monitoring immune responses in blood, a specific focus of the lab has been measuring cellular immunity at sites of infection, such as skin, the female genital tract, the cornea, and the trigeminal ganglia.  Homing markers identified with this approach are being followed up at the mechanistic level to understand how virus-specific T-cells primed by local infections are programmed to turn into memory cells that can rapidly return to these sites.  Innate immune responses to HSV-2 mediated by plasmacytoid dendritic cells contribute to homing molecule expression and are being correlated with HSV disease severity in a cross-sectional study.

 
The lab also supports translational research in HSV and HIV vaccines and therapeutics. We are doing mouse immunogenicity and efficacy studies in the HSV-2 system using antigens discovered in the lab with a variety of modern vaccine formats and adjuvants. Our lab has also tested candidate HSV-2 vaccines in phase I human clinical trials, performing T-cell immunogenicity studies on serially collected blood samples.  Immunity to poxviruses is being investigated to optimize their use as vaccine vectors for HIV, and for basic studies into T-cell memory.  International collections of HSV-2 isolates are being sequenced for variation in key T-cell recognition and drug target genes.  Finally, the tools of cellular immunity research are being applied to assist in malaria vaccine design.


PUBLICATIONS

Koelle DM, Magaret A, McClurkan CL, Remington ML, Warren T, Teofilovici F, Wald A.  2008.  Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naïve or HSV-2-infected subjects. Clinical and Vaccine Immunology 15:773-782.

Muller WJ, Dong L, Vilalta A, Byrd B, McClurkan CL, Margalith M, Gaell A, Liu C, Kaslow D, Sidney J, Sette A, Huang ML, Koelle DM.  2009.  Herpes simplex type 2 tegument proteins contain subdominant T-cellular epitopes detectable in mice after infection and DNA immunization.  Journal of General Virology, in press.

Jing L, Davies DH, Chong TM, Chun S, McClurkan CL, Huang J, Story BT, Molina DM, Hirst S, Felgner PL, Koelle DM.  2008.  An extremely diverse CD4 responses to vaccinia virus in humans is revealed by proteome-wide T-cell profiling.  Journal of Virology 82:7120-7134.

Koelle DM, Huang J, Hensel MT, McClurkan CL.  2006.  Innate immune responses to herpes simplex virus type 2 influence skin homing molecule expression by memory CD4+ lymphocytes.  Journal of Virology, 80:2863-2872.

Koelle DM, Corey L.  2008.  Herpes simplex: insights on pathogenesis and possible vaccines.  Annual Review of Medicine 59: 381-395.