John N Galgiani

John N Galgiani

Director, Valley Fever Center for Excellence
Member of the Graduate Faculty
Professor, BIO5 Institute
Professor, Immunobiology
Professor, Internal Medicine
Professor, Medicine
Primary Department
Department Affiliations
Contact
(520) 626-4968

Work Summary

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

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

Rex, J. H., Pfaller, M. A., Galgiani, J. N., Bartlett, M. S., EspinelIngroff, A., Ghannoum, M. A., Lancaster, M., Odds, F. C., Rinaldi, M. G., Walsh, T. J., & Barry, A. L. (1997). Development of interpretive breakpoints for antifungal susceptibility testing: Conceptual framework and analysis of in vitro in vivo correlation data for fluconazole, itraconazole, and Candida infections. CLINICAL INFECTIOUS DISEASES, 24(2), 235-247.
Wack, E. E., Ampel, N. M., Sunenshine, R. H., & Galgiani, J. N. (2015). The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 61(5), 787-91.

A skin test that detects dermal hypersensitivity in persons with past infection with Coccidioides species is again available for clinical use. Nearly all of the clinical studies with similar materials were published prior to the 1990s, and as a result, many practicing physicians will be unfamiliar with how skin testing for coccidioidomycosis might be useful in patient management or as a research tool. We review clinical and epidemiological studies with past skin test antigens, the composition of past and current skin test preparations with particular attention to differences in the preservatives, and how the current preparation could be used today.

Abuodeh, R. O., Galgiani, J. N., & Scalarone, G. M. (2002). Molecular approaches to the study of Coccidioides immitis. International journal of medical microbiology : IJMM, 292(5-6), 373-80.

The study of the molecular biology of Coccidioides sp. is only just beginning. As the importance of coccidioidomycosis grows as a public health problem, our need for understanding of pathogenesis, immune responses, and improved antifungal therapy also increases in proportion. Tools have now become available to study gene manipulation in this pathogen and this will allow molecular approaches to be used. Genetic experiments will also be accelerated by the availability of the whole coccidioidal genome, expected to be made public in the spring of 2003 (see http://www.tigr.org/tdb/tgi/cigi/GenInfo.html). Thus, there seems to be several reasons to expect considerable progress in the coming years.

Kellner, E. M., Orsborn, K. I., Siegel, E. M., Mandel, M. A., Orbach, M. J., & Galgiani, J. N. (2005). Coccidioides posadasii contains a single 1,3-beta-glucan synthase gene that appears to be essential for growth. Eukaryotic cell, 4(1), 111-20.

1,3-beta-Glucan synthase is responsible for the synthesis of beta-glucan, an essential cell wall structural component in most fungi. We sought to determine whether Coccidioides posadasii possesses genes homologous to known fungal FKS genes that encode the catalytic subunit of 1,3-beta-glucan synthase. A single gene, designated FKS1, was identified, and examination of its predicted protein product showed a high degree of conservation with Fks proteins from other filamentous fungi. FKS1 is expressed at similar levels in mycelia and early spherulating cultures, and expression decreases as the spherules mature. We used Agrobacterium-mediated transformation to create strains that harbor DeltaFKS1::hygB, a null allele of FKS1, and hypothesize that Fks1p function is essential, due to our inability to purify this allele away from a complementing wild-type FKS1 allele in a heterokaryotic strain. The heterokaryon appears normal with respect to growth rate and arthroconidium production; however, microscopic examination of strains with DeltaFKS1::hygB alleles revealed abnormal swelling of hyphal elements.

Shubitz, L. F., Yu, J., Hung, C., Kirkland, T. N., Peng, T., Perrill, R., Simons, J., Xue, J., Herr, R. A., Cole, G. T., & Galgiani, J. N. (2006). Improved protection of mice against lethal respiratory infection with Coccidioides posadasii using two recombinant antigens expressed as a single protein. Vaccine, 24(31-32), 5904-11.

Two recombinant antigens which individually protect mice from lethal intranasal infection were studied in combination, either as a mixture of two separately expressed proteins or as a single chimeric expression product. Mice vaccinated with either combination survived longer than mice given single antigens. Immunized mice also exhibited specific IgG immunoglobulins and yielded splenocytes which produced interferon-gamma in response to either antigen. The chimeric antigen has the practical advantage of offering enhanced protection from multiple components without increasing production costs.