John N Galgiani
Director, Valley Fever Center for Excellence
Professor, BIO5 Institute
Professor, Medicine
Primary Department
Department Affiliations
(520) 626-4968
Work Summary
Valley Fever (coccidioidomycosis) occurs more in Arizona than anywhere else. My research and others at the Valley Fever Center for Excellence involve understanding how disease is caused by infection, how the immune system stops or prevents illness, and how we can better diagnose, treat, or prevent this public health problem.
Research Interest
Dr. Galgiani has focused his career on Arizona’s special problems with Valley Fever. His work has included studies of the impact of Valley Fever on the general population and on special groups such as organ transplant recipients and patients with AIDS. For 19 years, as part of the NIH-sponsored Mycoses Study Group, Dr. Galgiani has been the project director of a coccidioidomycosis clinical trials group. Through collaboration, this group has evaluated new therapies for Valley Fever more rapidly and with greater clarity than might otherwise have been possible by investigators working in isolation. Dr. Galgiani has also been involved with efforts to prevent Valley Fever through vaccination. His group discovered and patented a recombinant antigen which is the basis for a vaccine candidate suitable for further development and clinical trials. Most recently, he has become the project leader for developing a new drug, nikkomycin Z, for treating Valley Fever. With recent NIH and FDA grant awards, clinical trials with this drug were resumed in 2007. Dr. Galgiani is also Chief Medical Officer of Valley Fever Solutions, Inc, a start-up company founded to assist in the drug’s development. In 1996, the Arizona Board of Regents accepted Dr. Galgiani’s proposal to establish the Valley Fever Center for Excellence for the Arizona universities. Based at the University of Arizona, the Center is pledged to spread information about Valley Fever, help patients with the severest complications of this disease, and to encourage research into the biology and diseases of its etiologic agent. The Center maintains a website (www.VFCE.Arizona.edu) and answers inquiries from health care professionals located in Arizona, other parts of the United States, and even from other countries. The Valley Fever Corridor Project, begun in 2009, intends to facilitate communication among Arizona clinicians to also improve patient care. In 2011, The Valley Fever Center in Phoenix was announced as a partnership between St. Joseph’s Hospital and the UA College of Medicine in Phoenix. It began operation in June, 2012. Research is increasing into the environmental biology of the fungus within its desert soil habitat as well as how the fungus caused disease and the body’s immunity controls it. Since Arizona has the only medical schools situated directly within the endemic region for Valley Fever, it is quite appropriate that Arizona lead in solving this problem. As Director of the Center, Dr. Galgiani is working for its full implementation as a means of ensuring an institutional commitment to accomplish this goal. Keywords: Coccidioidomycosis, Valley Fever, antifungal drugs, vaccines, serologic tests,

Publications

Noble, J. A., Nelson, R. G., Fufaa, G. D., Kang, P., Shafir, S. C., & Galgiani, J. N. (2016). Effect of Geography on the Analysis of Coccidioidomycosis-Associated Deaths, United States. Emerging infectious diseases, 22(10), 1821-3.

Because coccidioidomycosis death rates vary by region, we reanalyzed coccidioidomycosis-associated mortality in the United States by race/ethnicity, then limited analysis to Arizona and California. Coccidioidomycosis-associated deaths were shown to increase among African-Americans but decrease among Native Americans and Hispanics. Separately, in a Native American cohort, diabetes co-varied with coccidioidomycosis-associated death.

Galgiani, J. N. (2013). Elements of style in managing coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 56(11), 1586-8.
BRASS, C., GALGIANI, J. N., BLASCHKE, T. F., DEFELICE, R., OREILLY, R. A., & STEVENS, D. A. (1982). DISPOSITION OF KETOCONAZOLE, AN ORAL ANTIFUNGAL, IN HUMANS. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 21(1), 151-158.
Sampaio, E. P., Hsu, A. P., Pechacek, J., Bax, H. I., Dias, D. L., Paulson, M. L., Chandrasekaran, P., Rosen, L. B., Carvalho, D. S., Ding, L., Vinh, D. C., Browne, S. K., Datta, S., Milner, J. D., Kuhns, D. B., Long Priel, D. A., Sadat, M. A., Shiloh, M., De Marco, B., , Alvares, M., et al. (2013). Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis. The Journal of allergy and clinical immunology, 131(6), 1624-34.

Impaired signaling in the IFN-γ/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis.

Shubitz, L. F., Trinh, H. T., Perrill, R. H., Thompson, C. M., Hanan, N. J., Galgiani, J. N., & Nix, D. E. (2014). Modeling nikkomycin Z dosing and pharmacology in murine pulmonary coccidioidomycosis preparatory to phase 2 clinical trials. The Journal of infectious diseases, 209(12), 1949-54.

Nikkomycin Z (NikZ) is a chitin synthase inhibitor with activity against Coccidioides species that is being developed as a first-in-class orphan product for treatment of coccidioidomycosis. It has previously been shown to reduce lethal respiratory infections in mice to undetectable levels when treatment is begun 48 hours after infection. The studies described here focus on bracketing NikZ doses for phase 2 and 3 clinical trials, using an established mouse respiratory infection as a model and starting treatment 120 hours after infection. A dose of 80 mg/kg/day, divided into 2 doses, nearly eradicated infection, and larger doses did not improve fungal clearance. Increasing the duration of treatment from 1 week to 3 weeks resulted in a greater percentage of culture-negative mice. Comparative data show that plasma levels of NikZ that nearly eradicate Coccidioides in mice are achievable in patients and provide a plausibly effective dose range for initial phase 2 clinical studies.