John N Galgiani
- Director, Valley Fever Center for Excellence
- Professor, Medicine
- Professor, BIO5 Institute
- Clinical Professor, Internal Medicine - (Clinical Series Track)
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. He is currently leading a program to develop a live, avirulent vaccine candidate discovered by others at the UA. He is also the project leader for developing a new drug, nikkomycin Z, for treating Valley Fever. With 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. 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.
- M.D. Medicine
- Northwestern Medical School, Chicago, Illinois, United States
- B.S. Biology
- Stanford University, Palo Alto, California, United States
- Chief Medical Officer, Valley Fever Solutions, Inc (2007 - Ongoing)
- Director, Valley Fever Center for Excellence, University of Arizona, Tucson, Arizona (1996 - Ongoing)
- Professor with Tenure, University of Arizona, Tucson, Arizona (1990 - Ongoing)
- Associate Professor with Tenure, University of Arizona, Tucson, Arizona (1984 - 2009)
- Chief, Section of Infectious Diseases, Southern Arizona VA Health Care System (1978 - 2009)
- Assistant Professor of Medicine, University of Arizona, Tucson, Arizona (1978 - 1984)
- Fellow, Stanford University, Palo Alto, California (1974 - 1976)
- Infectious Diseases Society of America, Spring 1987
- American College of Physicians, Spring 1982
- Public Health Service Award
- Arizona Medical Society, Summer 2012
- Arizona Medical Association, Spring 2012
- Innovation Day Leading Edge Researcher
- University of Arizona, Fall 2008
- Founders Day Award
- UA COM-Tucson, Fall 2003
- University of Arizona College of Medicine, Fall 2003
- Achievement Award
- Coccidioidomycosis Study Group, Spring 2001
Licensure & Certification
- Medical Licensure, California, Medical Board of California (1973)
- Board Certification, American Board of Internal Medicine (1978)
- Medical Licensure, Arizona, Arizona Medical Board (1978)
No activities entered.
- Brown, H. E., Comrie, A. C., Tamerius, J., Khan, M., Tabor, J. A., & Galgiani, J. N. (2014). Climate, wind storms, and the risk of valley fever (coccidioidomycosis). In The Influence of Global Environmental Change on Infectious Disease Dynamics(pp Chapter A12). Washington, D.C.: The National Academies Press.
- Donovan, F., Malo, J., Zangeneh, T. T., & Galgiani, J. N. (2017). Top Questions in Diagnosis and Treatment of Coccidioidomycosis. Open Forum Infectious Diseases.
- Ganley, K. J., Bosch, P. R., Blair, J. E., Rischard, F., & Galgiani, J. N. (2017). Oxygen Consumption Deficits in Patients With Residual Fatigue After Primary Coccidioidomycosis. Open Forum Infectious Diseases, 4(3). doi:https://doi.org/10.1093/ofid/ofx136
- Odio, C. D., Marciano, B. E., Galgiani, J. N., & Holland, S. M. (2017). Risk Factors for Disseminated Coccidioidomycosis, United States. Emerging infectious diseases, 23(2).More infoOf 150,000 new coccidioidomycosis infections that occur annually in the United States, ≈1% disseminate; one third of those cases are fatal. Immunocompromised hosts have higher rates of dissemination. We identified 8 patients with disseminated coccidioidomycosis who had defects in the interleukin-12/interferon-γ and STAT3 axes, indicating that these are critical host defense pathways.
- Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Geertsma, F., Hoover, S. E., Johnson, R. H., Kusne, S., Lisse, J., MacDonald, J. D., Meyerson, S. L., Raksin, P. B., Siever, J., Stevens, D. A., Sunenshine, R., & Theodore, N. (2016). 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(6), e112-46.More infoIt is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.
- Narra, H. P., Shubitz, L. F., Mandel, M. A., Trinh, H. T., Griffin, K., Buntzman, A. S., Frelinger, J. A., Galgiani, J. N., & Orbach, M. J. (2016). A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection. Infection and immunity, 84(10), 3007-16.More infoThe CPS1 gene was identified as a virulence factor in the maize pathogen Cochliobolus heterostrophus Hypothesizing that the homologous gene in Coccidioides posadasii could be important for virulence, we created a Δcps1 deletion mutant which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-scid,γc(null) [NSG]). Only a single colony was recovered from 1 of 60 C57BL/6 mice following intranasal infections of up to 4,400 spores. Following administration of very high doses (10,000 to 2.5 × 10(7) spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 postinfection, but nearly all appeared degraded with infrequent endosporulation. Although the role of CPS1 in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in the Δcps1 strain versus C. posadasii is consistent with both metabolic and regulatory functions for the gene. The in vitro phenotype of the Δcps1 strain showed slower growth of mycelia with delayed and lower spore production than C. posadasii, and in vitro spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live Δcps1 spores either intranasally, intraperitoneally, or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens of
- 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.More infoBecause 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.
- Martirosyan, N. L., Skoch, J. M., Zaninovich, O., Zoccali, C., Galgiani, J. N., & Baaj, A. A. (2015). A paradigm for the evaluation and management of spinal coccidioidomycosis. Surgical neurology international, 6, 107.More infoCoccidioidomycosis is a fungal infection that is endemic to parts of the Southwestern United States. When infection involves the spine, the treatment strategies can be challenging. We have devised a management protocol for spinal coccidioidomycosis based on a review of the literature and our experience.
- Navalkar, K. A., Johnston, S. A., Woodbury, N., Galgiani, J. N., Magee, D. M., Chicacz, Z., & Stafford, P. (2014). Application of immunosignatures for diagnosis of valley fever. Clinical and vaccine immunology : CVI, 21(8), 1169-77.More infoValley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF false-negative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics.
- 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.More infoNikkomycin 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.
- Shubitz, L. F., Roy, M. E., Nix, D. E., & Galgiani, J. N. (2013). Efficacy of Nikkomycin Z for respiratory coccidioidomycosis in naturally infected dogs. Medical mycology, 51(7), 747-54.More infoNikkomycin Z (NikZ) is a chitin synthase inhibitor with antifungal efficacy against Coccidioides spp. and other endemic fungi. Dogs suffer a rate and range of natural coccidioidomycosis similar to humans and were considered an excellent model for initially testing NikZ against naturally acquired disease. Twelve dogs with coccidioidal pneumonia that had been present for an average of three months were treated with 250 mg (5-15 kg) or 500 mg (> 15-30 kg) twice daily for 60 days. Nine dogs completed the course of treatment and seven dogs had improvement in disease based on radiographs, clinicopathological parameters, physical examination findings, and subjective assessment by owners; three dogs had resolution or near resolution of disease. Based on this small study, NikZ shows efficacy to treat naturally acquired coccidioidomycosis and merits further development for trials in humans.
- Taroumian, S., Knowles, S. L., Lisse, J. R., Yanes, J., Ampel, N. M., Vaz, A., Galgiani, J. N., & Hoover, S. E. (2012). Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs. Arthritis care & research, 64(12), 1903-9.More infoCoccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona.
- Hector, R. F., Rutherford, G. W., Tsang, C. A., Erhart, L. M., McCotter, O., Anderson, S. M., Komatsu, K., Tabnak, F., Vugia, D. J., Yang, Y., & Galgiani, J. N. (2011). The public health impact of coccidioidomycosis in Arizona and California. International journal of environmental research and public health, 8(4), 1150-73.More infoThe numbers of reported cases of coccidioidomycosis in Arizona and California have risen dramatically over the past decade, with a 97.8% and 91.1% increase in incidence rates from 2001 to 2006 in the two states, respectively. Of those cases with reported race/ethnicity information, Black/African Americans in Arizona and Hispanics and African/Americans in California experienced a disproportionately higher frequency of disease compared to other racial/ethnic groups. Lack of early diagnosis continues to be a problem, particularly in suspect community-acquired pneumonia, underscoring the need for more rapid and sensitive tests. Similarly, the inability of currently available therapeutics to reduce the duration and morbidity of this disease underscores the need for improved therapeutics and a preventive vaccine.
- Shubitz, L. F., Dial, S. M., & Galgiani, J. N. (2011). T-lymphocyte predominance in lesions of canine coccidioidomycosis. Veterinary pathology, 48(5), 1008-11.More infoCoccidioidomycosis is a systemic fungal infection endemic to the southwestern United States. Although cell-mediated immunity is considered critical in control of the infection, little is known of the cellular population in naturally occurring lesions. To characterize the lymphocytic infiltration, archived formalin-fixed, paraffin-embedded tissues (subcutis, pericardium/heart, lung, bone, and synovium) from 18 dogs with coccidioidomycosis were studied with immunohistochemistry for CD3 and CD79a. In nearly all lesions, T lymphocytes were more numerous than B lymphocytes and were distributed throughout the lesion with concentration in the periphery of granulomas, whereas B lymphocytes were mostly confined to the periphery of granulomas. The predominance of T lymphocytes in lesions of canine coccidioidomycosis was independent of the tissue evaluated, the number of intralesional organisms, and the nature or severity of the inflammatory response.
- Neafsey, D. E., Barker, B. M., Sharpton, T. J., Stajich, J. E., Park, D. J., Whiston, E., Hung, C., McMahan, C., White, J., Sykes, S., Heiman, D., Young, S., Zeng, Q., Abouelleil, A., Aftuck, L., Bessette, D., Brown, A., FitzGerald, M., Lui, A., , Macdonald, J. P., et al. (2010). Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control. GENOME RESEARCH, 20(7), 938-946.
- Ostrosky-Zeichner, L., Casadevall, A., Galgiani, J. N., Odds, F. C., & Rex, J. H. (2010). An insight into the antifungal pipeline: selected new molecules and beyond. NATURE REVIEWS DRUG DISCOVERY, 9(9), 719-727.
- Ostrosky-Zeichner, L., Casadevall, A., Galgiani, J. N., Odds, F. C., & Rex, J. H. (2010). An insight into the antifungal pipeline: selected new molecules and beyond. Nature reviews. Drug discovery, 9(9), 719-27.More infoInvasive fungal infections are increasing in incidence and are associated with substantial mortality. Improved diagnostics and the availability of new antifungals have revolutionized the field of medical mycology in the past decades. This Review focuses on recent developments in the antifungal pipeline, concentrating on promising candidates such as new azoles, polyenes and echinocandins, as well as agents such as nikkomycin Z and the sordarins. Developments in vaccines and antibody-based immunotherapy are also discussed. Few therapeutic products are currently in active development, and progression of therapeutic agents with fungus-specific mechanisms of action is of key importance.
- Ampel, N. M., Dionne, S. O., Giblin, A., Podany, A. B., & Galgiani, J. (2009). Mannose-binding lectin serum levels are low in persons with clinically active coccidioidomycosis. Mycopathologia, 167(4), 173-80.More infoMannose-binding lectin (MBL) is a circulating collectin that is part of the innate immune response. We explored the serum levels of MBL in persons with different forms of coccidioidomycosis.
- Ampel, N. M., Giblin, A., Mourani, J. P., & Galgiani, J. N. (2009). Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 48(2), 172-8.More infoStudies that assess the value of initiating oral antifungal therapy to treat primary pulmonary coccidioidomycosis have not been published previously.
- Sharpton, T. J., Stajich, J. E., Rounsley, S. D., Gardner, M. J., Wortman, J. R., Jordar, V. S., Maiti, R., Kodira, C. D., Neafsey, D. E., Zeng, Q., Hung, C., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M. A., Kellner, E. M., Barker, B. M., Galgiani, J. N., Orbach, M. J., , Kirkland, T. N., et al. (2009). Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives. GENOME RESEARCH, 19(10), 1722-1731.
- Sharpton, T. J., Stajich, J. E., Rounsley, S. D., Gardner, M. J., Wortman, J. R., Jordar, V. S., Maiti, R., Kodira, C. D., Neafsey, D. E., Zeng, Q., Hung, C., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M. A., Kellner, E. M., Barker, B. M., Galgiani, J. N., Orbach, M. J., , Kirkland, T. N., et al. (2009). Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives. Genome research, 19(10), 1722-31.More infoWhile most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.
- Vinh, D. C., Masannat, F., Dzioba, R. B., Galgiani, J. N., & Holland, S. M. (2009). Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 49(6), e62-5.More infoSevere coccidioidomycosis is rare, and specific genetic susceptibility to the disease remains unidentified. We describe a patient with disseminated recalcitrant coccidioidomycosis with autosomal dominant interferon-gamma receptor 1 deficiency caused by a heterozygous IFNGR1 818del4 mutation. Therefore, the interleukin-12/interferon-gamma axis appears to be critical for control of coccidioidomycosis.
- Galgiani, J. N. (2008). Vaccines to prevent systemic mycoses: holy grails meet translational realities. The Journal of infectious diseases, 197(7), 938-40.
- Shubitz, L. F., Dial, S. M., Perrill, R., Casement, R., & Galgiani, J. N. (2008). Vaccine-induced cellular immune responses differ from innate responses in susceptible and resistant strains of mice infected with Coccidioides posadasii. Infection and immunity, 76(12), 5553-64.More infoSusceptibility to Coccidioides spp. varies widely in humans and other mammals and also among individuals within a species. Among strains of mice with various susceptibilities, immunohistopathology revealed that C57BL/6 mice were highly susceptible to the disease following intranasal infection, DBA/2n mice were intermediate, and Swiss-Webster mice were innately resistant. Resistant Swiss-Webster mice developed prominent perivascular/peribronchiolar lymphocytic cuffing and well-formed granulomas with few fungal elements and debris in the necrotic center, surrounded by a mantle of macrophages, lymphocytes, and fibrocytes. Susceptible C57BL/6 mice became moribund between 14 and 18 days postinfection, with overwhelming numbers of neutrophils and spherules and very few T cells, the drastic reduction of which was associated with failure and death, while intermediate DBA/2n mice controlled the fungal burden but demonstrated progressive lung inflammation with prominent suppuration, and they deteriorated clinically. Vaccinated C57BL/6 mice had an early and robust lymphocyte response, which included significantly higher Mac2(+), CD3(+), and CD4(+) cell scores on day 18 than those of innately resistant SW mice and DBA/2n mice; they also had prominent perivascular/peribronchiolar lymphocytic infiltrates not present in their unvaccinated counterparts, and they appeared to be resolving lesions by day 56 compared to the other two strains, based on significantly lower disease scores and observably smaller and fewer lesions with few spherules and neutrophils.
- Johnson, S. M., Lerche, N. W., Pappagianis, D., Yee, J. L., Galgiani, J. N., & Hector, R. F. (2007). Safety, antigenicity, and efficacy of a recombinant coccidioidomycosis vaccine in cynomolgus macaques (Macaca fascicularis). Annals of the New York Academy of Sciences, 1111, 290-300.More infoThe safety, immunogenicity and efficacy of recombinant Ag2/PRA106 + CSA chimeric fusion protein (CFP) vaccine in ISS/Montanide adjuvant-administered intramuscular (IM) was assessed in adult female cynomolgus macaques challenged with Coccidioides posadasii. Animals received three immunizations with either 5 microg CFP, 50-microg CFP, or adjuvant alone and were challenged 4 weeks following the final immunization. Although significant antibody response was produced in response to vaccination, there were no discernable adverse effects, suggesting that the vaccine was well tolerated. Upon intratracheal challenge, all animals showed evidence of disease. Two animals that received 5-microg doses of CFP were euthanatized prior to the study's end because of severe symptoms. Animals vaccinated with 50-microg doses of CFP showed evidence of enhanced sensitization compared to adjuvant controls and animals vaccinated with 5-microg doses of CFP. This was based on higher serum anti-CFP titers, enhanced secretion of interferon-gamma (IFN-gamma) from stimulated bronchoalveolar lavage mononuclear cells (BALMC), reduced pulmonary radiologic findings following intratracheal challenge, reduced terminal complement fixation titers, and reduced necropsy findings. Overall the vaccine was well tolerated, induced sensitization, and resulted in a protective response when given at the higher 50-microg dose. Additional experiments may be needed to optimize the vaccination and to confer greater protection against lethal challenge.
- Rohrbough, J. G., Galgiani, J. N., & Wysocki, V. H. (2007). The application of proteomic techniques to fungal protein identification and quantification. Annals of the New York Academy of Sciences, 1111, 133-46.More infoThe number of sequenced genomes has increased rapidly in the last few years, supporting a revolution in bioinformatics that has been leveraged by scientists seeking to analyze the proteomes of numerous biological systems. The primary technique employed for the identification of peptides and proteins from biological sources is mass spectrometry (MS). This analytical process is usually in the form of whole-protein analysis (termed "top-down" proteomics) or analysis of enzymatically produced peptides (known as the "bottom-up" approach). This article will focus primarily on the more common bottom-up proteomics to include topics such as sample preparation, separation strategies, MS instrumentation, data analysis, and techniques for protein quantification. Strategies for preparation of samples for proteomic analysis, as well as tools for protein and peptide separation will be discussed. A general description of common MS instruments along with tandem mass spectrometry (MS/MS) will be given. Different methodologies of sample ionization including matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) will be discussed. Data analysis methods including database search algorithms and tools for protein sequence analysis will be introduced. We will also discuss experimental strategies for MS protein quantification using stable isotope labeling techniques and fluorescent labeling. We will introduce several fungal proteomic studies to illustrate the use of these methods. This article will allow investigators to gain a working knowledge of proteomics along with some strengths and weaknesses associated with the techniques presented.
- Mandel, M. A., Galgiani, J. N., Kroken, S., & Orbach, M. J. (2006). Coccidioides posadasii contains single chitin synthase genes corresponding to classes I to VII. Fungal genetics and biology : FG & B, 43(11), 775-88.More infoCoccidioides posadasii is a dimorphic fungal pathogen of humans and other mammals. The switch between saprobic and parasitic growth involves synthesis of new cell walls of which chitin is a significant component. To determine whether particular subsets of chitin synthases (CHSes) are responsible for production of chitin at different stages of differentiation, we have isolated six CHS genes from this fungus. They correspond, together with another reported CHS gene, to single members of the seven defined classes of chitin synthases (classes I-VII). Using Real-Time RT-PCR we show their pattern of expression during morphogenesis. CpCHS2, CpCHS3, and CpCHS6 are preferentially expressed during the saprobic phase, while CpCHS1 and CpCHS4 are more highly expressed during the parasitic phase. CpCHS5 and CpCHS7 expression is similar in both saprobic and parasitic phases. Because C. posadasii contains single members of the seven classes of CHSes found in fungi, it is a good model to investigate the putatively different roles of these genes in fungal growth and differentiation.
- Orsborn, K. I., Shubitz, L. F., Peng, T., Kellner, E. M., Orbach, M. J., Haynes, P. A., & Galgiani, J. N. (2006). Protein expression profiling of Coccidioides posadasii by two-dimensional differential in-gel electrophoresis and evaluation of a newly recognized peroxisomal matrix protein as a recombinant vaccine candidate. Infection and immunity, 74(3), 1865-72.More infoCoccidioides posadasii and Coccidioides immitis are dimorphic, soil-dwelling pathogenic ascomycetes endemic to the southwestern United States. Infection can result from inhalation of a very few arthroconidia, but following natural infection, long-lived immunity is the norm. Previous work in the field has shown that spherule-derived vaccines afford more protection than those from mycelia. We have used two-dimensional differential in-gel electrophoresis coupled with nano-high-performance liquid chromatography-tandem mass spectrometry to directly assess both absolute abundance and differential expression of proteins in the spherule and the mycelial phases of C. posadasii with the intent to identify potential vaccine candidates. Peptides derived from 40 protein spots were analyzed and a probable identity was assigned to each. One spherule-abundant protein, identified as Pmp1, showed homology to allergens from Aspergillus fumigatus and other fungi, all of which exhibit similarity to yeast thiol peroxidases. Recombinant Pmp1 was reactive with serum from individuals with both acute and protracted disease, and evoked protection in two murine models of infection with C. posadasii. These results demonstrate the utility of proteomic analysis as a point of discovery for protective antigens for possible inclusion in a vaccine candidate to prevent coccidioidomycosis.
- Valdivia, L., Nix, D., Wright, M., Lindberg, E., Fagan, T., Lieberman, D., Stoffer, T., Ampel, N. M., & Galgiani, J. N. (2006). Coccidioidomycosis as a common cause of community-acquired pneumonia. Emerging infectious diseases, 12(6), 958-62.More infoThe early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%-44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism.
- Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Johnson, R. H., Stevens, D. A., & Williams, P. L. (2005). Coccidioidomycosis. CLINICAL INFECTIOUS DISEASES, 41(9), 1217-1223.
- Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Johnson, R. H., Stevens, D. A., Williams, P. L., & , I. D. (2005). Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 41(9), 1217-23.
- 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.More info1,3-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.
- Park, B. J., Sigel, K., Vaz, V., Komatsu, K., McRill, C., Phelan, M., Colman, T., Comrie, A. C., Warnock, D. W., Galgiani, J. N., & Hajjeh, R. A. (2005). An epidemic of coccidioidomycosis in Arizona associated with climatic changes, 1998-2001. The Journal of infectious diseases, 191(11), 1981-7.More infoReports of coccidioidomycosis cases in Arizona have increased substantially. We investigated factors associated with the increase.
- Chiller, T. M., Galgiani, J. N., & Stevens, D. A. (2003). Coccidioidomycosis. INFECTIOUS DISEASE CLINICS OF NORTH AMERICA, 17(1), 41-+.
- 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.More infoThe 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.
- Galgiani, J. N., Ampel, N. M., Catanzaro, A., Johnson, R. H., Stevens, D. A., & Williams, P. L. (2000). Practice guidelines for the treatment of coccidioidomycosis. CLINICAL INFECTIOUS DISEASES, 30(4), 658-661.
- 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.
- Fridkin, S. K., Pear, S. M., Williamson, T. H., Galgiani, J. N., & Jarvis, W. R. (1996). The role of understaffing in central venous catheter-associated bloodstream infections. INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY, 17(3), 150-158.
- Ghannoum, M. A., Rex, J. H., & Galgiani, J. N. (1996). Susceptibility testing of fungi: Current status of correlation of in vitro data with clinical outcome. JOURNAL OF CLINICAL MICROBIOLOGY, 34(3), 489-495.
- REX, J. H., COOPER, C. R., MERZ, W. G., GALGIANI, J. N., & ANAISSIE, E. J. (1995). DETECTION OF AMPHOTERICIN B-RESISTANT CANDIDA ISOLATES IN A BROTH-BASED SYSTEM. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 39(4), 906-909.
- DENNING, D. W., LEE, J. Y., HOSTETLER, J. S., PAPPAS, P., KAUFFMAN, C. A., DEWSNUP, D. H., GALGIANI, J. N., GRAYBILL JR, ., SUGAR, A. M., CATANZARO, A., GALLIS, H., PERFECT JR, ., DOCKERY, B., DISMUKES, W. E., & STEVENS, D. A. (1994). NIAID MYCOSES STUDY-GROUP MULTICENTER TRIAL OF ORAL ITRACONAZOLE THERAPY FOR INVASIVE ASPERGILLOSIS. AMERICAN JOURNAL OF MEDICINE, 97(2), 135-144.
- PEAR, S. M., WILLIAMSON, T. H., BETTIN, K. M., GERDING, D. N., & GALGIANI, J. N. (1994). DECREASE IN NOSOCOMIAL CLOSTRIDIUM-DIFFICILE-ASSOCIATED DIARRHEA BY RESTRICTING CLINDAMYCIN USE. ANNALS OF INTERNAL MEDICINE, 120(4), 272-277.
- FROMTLING, R. A., GALGIANI, J. N., PFALLER, M. A., ESPINELINGROFF, A., BARTIZAL, K. F., BARTLETT, M. S., BODY, B. A., FREY, C., HALL, G., ROBERTS, G. D., NOLTE, F. B., ODDS, F. C., RINALDI, M. G., SUGAR, A. M., & VILLAREAL, K. (1993). MULTICENTER EVALUATION OF A BROTH MACRODILUTION ANTIFUNGAL SUSCEPTIBILITY TEST FOR YEASTS. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 37(1), 39-45.
- GALGIANI, J. N., CATANZARO, A., CLOUD, G. A., HIGGS, J., FRIEDMAN, B. A., LARSEN, R. A., & GRAYBILL JR, . (1993). FLUCONAZOLE THERAPY FOR COCCIDIOIDAL MENINGITIS. ANNALS OF INTERNAL MEDICINE, 119(1), 28-35.
- REX, J. H., PFALLER, M. A., RINALDI, M. G., POLAK, A., & GALGIANI, J. N. (1993). ANTIFUNGAL SUSCEPTIBILITY TESTING. CLINICAL MICROBIOLOGY REVIEWS, 6(4), 367-381.
- ESPINELINGROFF, A., KISH, C. W., KERKERING, T. M., FROMTLING, R. A., BARTIZAL, K., GALGIANI, J. N., VILLAREAL, K., PFALLER, M. A., GERARDEN, T., RINALDI, M. G., & FOTHERGILL, A. (1992). COLLABORATIVE COMPARISON OF BROTH MACRODILUTION AND MICRODILUTION ANTIFUNGAL SUSCEPTIBILITY TESTS. JOURNAL OF CLINICAL MICROBIOLOGY, 30(12), 3138-3145.
- FISH, D. G., AMPEL, N. M., GALGIANI, J. N., DOLS, C. L., KELLY, P. C., JOHNSON, C. H., PAPPAGIANIS, D., EDWARDS, J. E., WASSERMAN, R. B., CLARK, R. J., ANTONISKIS, D., LARSEN, R. A., ENGLENDER, S. J., & PETERSEN, E. A. (1990). COCCIDIOIDOMYCOSIS DURING HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - A REVIEW OF 77 PATIENTS. MEDICINE, 69(6), 384-391.
- PFALLER, M. A., RINALDI, M. G., GALGIANI, J. N., BARTLETT, M. S., BODY, B. A., ESPINELINGROFF, A., FROMTLING, R. A., HALL, G. S., HUGHES, C. E., ODDS, F. C., & SUGAR, A. M. (1990). COLLABORATIVE INVESTIGATION OF VARIABLES IN SUSCEPTIBILITY TESTING OF YEASTS. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 34(9), 1648-1654.
- BRONNIMANN, D. A., ADAM, R. D., GALGIANI, J. N., HABIB, M. P., PETERSEN, E. A., PORTER, B., & BLOOM, J. W. (1987). COCCIDIOIDOMYCOSIS IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME. ANNALS OF INTERNAL MEDICINE, 106(3), 372-379.
- ROGERS, T. E., & GALGIANI, J. N. (1986). ACTIVITY OF FLUCONAZOLE (UK-49,858) AND KETOCONAZOLE AGAINST CANDIDA-ALBICANS INVITRO AND INVIVO. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 30(3), 418-422.
- PONT, A., GRAYBILL JR, ., CRAVEN, P. C., GALGIANI, J. N., DISMUKES, W. E., REITZ, R. E., & STEVENS, D. A. (1984). HIGH-DOSE KETOCONAZOLE THERAPY AND ADRENAL AND TESTICULAR FUNCTION IN HUMANS. ARCHIVES OF INTERNAL MEDICINE, 144(11), 2150-2153.
- 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.
- DEFELICE, R., JOHNSON, D. G., & GALGIANI, J. N. (1981). GYNECOMASTIA WITH KETOCONAZOLE. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 19(6), 1073-1074.
- GALGIANI, J. N., & STEVENS, D. A. (1976). ANTIMICROBIAL SUSCEPTIBILITY TESTING OF YEASTS - TURBIDIMETRIC TECHNIQUE INDEPENDENT OF INOCULUM SIZE. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 10(4), 721-726.
- LUTWICK, L. I., GALGIANI, J. N., JOHNSON, R. H., & STEVENS, D. A. (1976). VISCERAL FUNGAL INFECTIONS DUE TO PETRIELLIDIUM BOYDII (ALLESCHERIA BOYDII) - INVITRO DRUG SENSITIVITY STUDIES. AMERICAN JOURNAL OF MEDICINE, 61(5), 632-640.
- Butkiewicz, C. D., Lewis, M. L., Trinh, H. T., Galgiani, J. N., Shubitz, L., Frelinger, J. A., & Orbach, M. J. (2017, August). Further characterization of the avirulent delta-cps1 Coccidioides vaccine in mice. Seventh International Coccidioidomycosis Symposium. Stanford University, Stanford, CA: Stanford Center for Continuing Medical Education.More infoPoster presentation on further analysis of the duration and protection of the delta-cps1 valley fever vaccine.
- Frelinger, J. A., Galgiani, J. N., Orbach, M. J., D, B. C., Trinh, H. T., Lewis, M. L., Shubitz, L., & Powell, D. A. (2017, August). Determining Mechanisms of Protection in a Live Attenuated Coccidiodes Vaccine. 7th International Coccidioidomycosis Symposium. Stanford University, Stanford, CA: Stanford Center for Continuing Medical Education.More infoposter presentation describing the immune response of mice to our valley fever vaccine.
- Lussier, Y. A., Galgiani, J. N., Frelinger, J. A., Holland, S. M., Hsu, A., Powell, D., Li, H., Li, Q., & Berghout, J. (2017, August). SINGLE-SUBJECT TRANSCRIPTOME PROFILING OF STAT4 MUTANT PATIENT PBMCS SUGGESTS ALTERED RESPONSIVENESS TO COCCI LYSATE STIMULATION. PROCEEDINGS OF THE COCCIDIOIDOMYCOSIS STUDY GROUP 61st ANNUAL MEETING in collaboration with the 7th INTERNATIONAL COCCIDIOIDOMYCOSIS SYMPOSIUM. Stanford University.
- Orbach, M. J., Galgiani, J. N., Frelinger, J. A., Buntzman, A. S., Trinh, H., Lewis, L., Shubitz, L., & Mandel, M. A. (2017, March, 2017). Construction and Efficacy of delta-cps1, a live attenuated vaccine for coccidioidomycosis. 29th Fungal Genetics Conference. Asilomar Conference Center, Pacific Grove, CA: Genetics Society of America.More infoA poster was presented, and was selected for a poster talk in the Concurrent Session "Human Pathogenic Fungi", which was presented by Dr. Mandel.The abstracts are published as a supplement of Fungal Genetics Reports.
- Orbach, M. J., Galgiani, J. N., Frelinger, J. A., Buntzman, A., Lewis, M. L., Trinh, H., Shubitz, L., & Mandel, M. A. (2017, April 1). Construction and efficacy of delta-cps1, a live attenuated vaccine for coccidioidomycosis. 56th Annual ASM Regional Meeting- Southwest Region. University of Arizona: American Society of Microbiology.