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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
  • Joint Professor, Laboratory Medicine
  • Affiliate Investigator
  • Fred Hutchinson Cancer Research Center and Benaroya Research Institute

T-cell immunology is at the core of infectious diseases, cancer, and allergy. Our lab is fortunate to be able to work in each of these areas. We have funded programs in antigen identification and prioritization for herpes simplex viruses types 1 and 2, varicella zoster virus, and vaccinia (the vaccine for smallpox). In 2008, Merkel cell polyoma virus (MCPyV) was discovered as the cause of Merkel cell carcinoma (MCC). We've been actively collaborating with the leading MCC clinical group to develop therapies focusing on improving the immune response to the oncogenic viral protein. For Mycobacterium tuberculosis (MTB), I am responsible for the IGRA testing at our medical center, and have mentored several trainees interested in this unique application of T-cell immunology to clinical testing. The pathogens we work on 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 s ets 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, TCR expression, etc. are in use to measure several variables in the T-cell response. HSV-1 and HSV-2 vaccine candidates have been identified and studied in mice, and some have entered phase I-II human trials. Our group also performs clinical immune monitoring for clinical trials of candidate HSV vaccines. Recently, we have begun collaborative work with investigators interested in drug-related cutaneous toxicity (SJS-TEN reactions) mediated by CD8 T-cells.

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. We have funding for VZV and vaccinia, and also in the drug allergy area. The translational pipeline from natural history and vaccine candidate discovery to preclinical animal work to clinical trials is fully implemented, 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

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

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

Laing KJ, Russell RM, Dong L, Schmid DS, Stern M, Magaret A, Haas J, Johnston C, Wald A, Koelle DM.  2015.  Zoster vaccination increases the breadth of CD4+ T-cell responses to varicella zoster virus.  Journal of Infectious Diseases, ePub March 17, 2015. PMCID: 25784732.
PubMed Abstract

Nayak K, Jing L, Russell RM, Davies DH, Hermanson G, Molina DM, Liang X, Sherman DR, Kwok WW, Yang J, Kenneth J, Ahamed SF, Chandele A, Kaja M-K, Koelle DM.  2015.  Identification of novel Mycobacterium tuberculosis CD4 T-cell antigens via high throughput proteome scanning.  Tuberculosis, ePub March 26, 2015. PMCI:D 25857935.
PubMed Abstract

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