Thomas Kozel, Ph.D.
Department of Microbiology and Immunology
University of Nevada School of Medicine
Doctoral degree in Microbiology, 1971, University of Iowa
Mail Stop: 320
Dr. Kozel’s interests include the pathogenesis of fungal infection, the immune response to capsular polysaccharides, opportunistic infections, particularly infections associated with HIV/AIDS, and biodefense. Recent studies are focused on diagnostics for the developing world.
There are currently four NIH-funded studies in the Kozel laboratory. First, we are developing immunoassays for early diagnosis of anthrax. This is a mature study that is in the advanced stages of product development. Second, we are developing immunoassays for diagnosis of invasive aspergillosis. This study recently received a major second round of NIH funding. Third, the Kozel laboratory is producing antibodies that can be used for diagnosis of other fungal infections such as disseminated histoplasmosis. Finally, a major effort is directed toward study of antibodies specific for the capsular polypeptide of Bacillus anthracis. These studies aim to understand the mechanisms of protection by anticapsular antibodies in inhalational anthrax.
A central theme in the Kozel laboratory is understanding how antibodies function in diagnostic tests. What are the properties of the ideal antibody? Can we identify effective diagnostic antibodies early in the development process such that time to product and discovery cost are minimized? Can antibodies be modified to improve assay performance? Do different assay platforms, e.g., enzyme immunoassay vs. lateral flow immunoassay, place different requirements on antibody performance?
The approach and outcome of diagnostics development is illustrated by the recently developed lateral flow assay for diagnosis of cryptococcal meningitis. Cryptococcal meningitis kills more than 500,000 people with HIV/AIDS per year in sub-Saharan Africa alone, more than the number of deaths attributed to tuberculosis. Termed CrAg LFA, the test detects cryptococcal antigen (CrAg) using a dipstick or lateral flow assay (LFA) format. The CrAg LFA was developed by Immuno-Mycologics using third-generation monoclonal antibodies from the Kozel laboratory. The test was recently cleared by the FDA and is recommended for use by the World Health Organization. The CDC has estimated that use of the test can save 50,000 to 100,000 lives each year.
Kozel, T.R., W.J. Murphy, S. Brandt, B.R. Blazar, J.A. Lovchik, P. Thorkildson, A. Percival and C.R. Lyons. 2004. mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia. Proc. Natl. Acad. Sci. U.S.A. 101:5042-5047.
Gates-Hollingsworth, M.A., and T.R. Kozel. 2009. Phenotype heterogeneity in expression of epitopes in the Cryptococcus neoformans capsule. Mol. Microbiol. 74:126-138 (Cover photograph).
Nuti, D.E., R.B. Crump, F.Dwi Handayani, N. Chantratita, S.J. Peacock, R. Bowen, P.L. Felgner, D.Huw Davies, T. Wu, C.R. Lyons, P.J. Brett, M.N. Burtnick, T.R. Kozel, and D.P. AuCoin. 2011. Identification of circulating bacterial antigens by in vivo microbial antigen discovery. mBio. Pii: e00136-11. Doi: 10.1128/mBio.00136-11(Editors pick).
Jarvis, J.N., A. Percival, S. Bauman, J. Pelfrey, G. Meintjes, G.N. Williams, N. Longley, T.S. Harrison and T.R. Kozel. 2011. Evaluation of a novel point of care cryptococcal antigen test on serum, plasma and urine from patients with HIV-associated cryptococcal meningitis. Clin. Infect. Dis. 53:1019-1023.