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Directory >> David M. Koelle, MD

Faculty

David M. Koelle, MD

  • Professor, Division of Allergy and Infectious Diseases
  • Adjunct Professor, Global Health and Laboratory Medicine
  • University of Washington
  • Affiliate Investigator
  • Fred Hutchinson Cancer Research Center

How can we make a herpes vaccine? Improve the shingles vaccine? Why do some people have severe herpes? We study immune responses to infections, pathogen genetic variation, and the relationship between host genomics, immune responses, and infection severity. Pathogens include herpes simplex viruses types 1 and 2, varicella zoster virus, vaccinia (the vaccine for smallpox), Merkel cell polyoma virus (MCPyV), and Mycobacterium tuberculosis (MTB). These agents mostly have large genomes, so determining the antigens that elicit T-cell responses is challenging. Our technical expertise is the use of genomic libraries and genome-spanning ORF sets to interrogate CD8 and CD4 T-cell responses to a very high level of definition. A suite of modern immunology tools such as intracellular cytokine cytometry, tetramers, cell killing assays, etc. are in use to measure several variables in the T-cell response. HSV-1 and HSV-2 vaccine candidates have been identified. We've had the chance to study some of these in mice, and some have entered phase I-II human trials. Our group works closely with faculty at the Virology Research Clinic located at Harborview, and is integrated with the UW Clinical Virology lab.

Recently, we are assisting oncologists to decode the T cell response to MCPyV to assist cancer therapy, and we are participating in a discovery project to identify new tumor-specific antigens. Another newer set of projects in the lab involve assisting non-governmental organizations to create and evaluate more stable and potent versions of established vaccines, for example rotavirus, polio, and influenza. Some of this work is done in mouse models. Newer initiatives also include studies of T-cell diversity using regular and deep sequencing of TCR hypervariable regions, studies of HSV-1 and HSV-2 sequence diversity at the DNA level, and detailed study of long-term T-cell memory decades after vaccination or infection. The clinical lab runs the T-cell IGRA test for MTB, and we have an epitope discovery initiative for MTB.

Fellows interested in modern laboratory immunology are welcome in the lab. The most consistent funding and deepest experience is with HSV, but projects on other pathogens are also possible. The translational pipeline from candidate discovery to preclinical animal work to natural history research and finally to clinical trials is active between our lab and our collaborators' groups. Projects within or spanning these phases are available. Search Pubmed on "Koelle DM".


Selected Publications


Jing L, Haas J, Chong TM, Bruckner JJ, Dann GC, Dong L, Marshak JO, McClurkan CL, Yamamoto TN, Bailer SM, Laing KJ, Wald A, Verjans GM, Koelle DM. Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. J Clin Invest. 2012; 122(2): 654-73. doi: 10.1172/JCI60556. PMID: 22214845
PubMed Abstract


Moss NJ, Magaret A, Laing KJ, Kask AS, Wang M, Mark KE, Schiffer JT, Wald A, Koelle DM. Peripheral blood CD4 T-cell and plasmacytoid dendritic cell (pDC) reactivity to herpes simplex virus 2 and pDC number do not correlate with the clinical or virologic severity of recurrent genital herpes. J Virol. 2012; 86(18): 9952-63. doi: 10.1128/JVI.00829-12. PMID: 22761381.
• PubMed Abstract


Jing L, Schiffer JT, Chong TM, Bruckner JJ, Davies DH, Felgner PL, Haas J, Wald A, Verjans GM, Koelle DM. CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence. J Virol. 2013; 87(5): 2617-27.
doi: 10.1128/JVI.03047-12. PMID:  23255792.
PubMed Abstract


van Velzen M, Jing L, Osterhaus ADME, Sette A, Koelle DM*, Verjans GMGM* (*Co-senior author). 2013. Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in human ganglia. PLoS Pathogens 9:e1003547. PMID:23966859. PMCID: PMC3744444.
PubMed Abstract


Dutton JL, Li B, Woo W-P, Marshak JO, Xu Y, Huang M-L, Dong L, Frazer IH, Koelle DM. 2013. A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice. PLoS One 8:e76407. PMID:24098493. PMCID: PMC3789751.
PubMed Abstract


Chapuis AG, Afanasiev O, Iyer J, Paulson KG, Parvathaneni U, Hwang JH, Lai I, Roberts IM, Sloan HL, Bhatia S, Shibuya K, Gooley T, Desmarais C, Koelle DM., Yee C, Nghiem P. 2014. Regression of metastatic Merkel cell carcinoma following transfer of polyoma-specific T-cells and therapies capable of re-inducing HLA class. Cancer Immunology Research 2: 27-36. PMID: 24432305.
PubMed Abstract

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