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".
Watch Dr. Koelle's 2015 lecture on "Laboratory Evaluation of Immunity to Mycobacterium Tuberculosis in Humans"
Worldwide circulation of HSV-2 × HSV-1 recombinant strains.
Koelle DM, Norberg P, Fitzgibbon MP, Russell RM, Greninger AL, Huang ML, Stensland L, Jing L, Magaret AS, Diem K, Selke S, Xie H, Celum C, Lingappa JR, Jerome KR, Wald A, Johnston C.
Sci Rep. 2017 Mar 13;7:44084. doi: 10.1038/srep44084. PMID: 28287142
Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival.
Miller NJ, Church CD, Dong L, Crispin D, Fitzgibbon MP, Lachance K, Jing L, Shinohara M, Gavvovidis I, Willimsky G, McIntosh M, Blankenstein T, Koelle DM, Nghiem P.
Cancer Immunol Res. 2017 Feb;5(2):137-147. doi: 10.1158/2326-6066.CIR-16-0210. Epub 2017 Jan 16. PMID: 28093446
Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.
Posavad CM, Zhao L, Dong L, Jin L, Stevens CE, Magaret AS, Johnston C, Wald A, Zhu J, Corey L, Koelle DM.
Mucosal Immunol. 2017 Jan 4. doi: 10.1038/mi.2016.118. [Epub ahead of print] PMID: 28051084
Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses.
Jing L, Laing KJ, Dong L, Russell RM, Barlow RS, Haas JG, Ramchandani MS, Johnston C, Buus S, Redwood AJ, White KD, Mallal SA, Phillips EJ, Posavad CM, Wald A, Koelle DM.
J Immunol. 2016 Mar 1;196(5):2205-18. doi: 10.4049/jimmunol.1502366. Epub 2016 Jan 25. PMID: 26810224
Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia.
van Velzen M, Jing L, Osterhaus ADME, Sette A, Koelle DM*, Verjans GMGM* (*Co-senior author). 2013. PLoS Pathogens 9:e1003547. PMID:23966859. PMCID: PMC3744444.
Identification of novel Mycobacterium tuberculosis CD4 T-cell antigens via high throughput proteome screening.
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. Tuberculosis, ePub March 26, 2015. PMCI:D 25857935.