# Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis

> **NIH NIH U01** · UNIVERSITY OF ARIZONA · 2020 · $563,465

## Abstract

Project Summary
Coccidioidomycosis (Valley Fever) is a serious public health problem for the Southwestern United States and
all who visit there. A small proportion of infections result in progressive, debilitating, even life-threatening
illness (disseminated coccidioidomycosis or DCM). All evidence suggests that this heightened susceptibility is
due to differences in immunologic responses of the patient, clearly understood in overtly immunodeficient
persons (i.e., those with AIDS) but not understood for the large majority of otherwise healthy patients with
DCM. The NIAID intramural PI (Dr. Steven Holland) has identified inheritable gene mutations in a few patients
each of which are associated with DCM. He has also found additional patients with DCM to have rare gene
variants possibly producing deleterious consequences. These discoveries provide clues to the pathways that
might be deregulated in other patients with DCM but who do not have such readily identifiable genetic
alternations. This project builds on the ongoing collaboration between Dr. Holland and Dr. John Galgiani,
University of Arizona (UA) Director of the Valley Fever Center for Excellence, to maintain a referral path for
subjects living in Arizona to the existing program at the NIH Clinical Center. This work will better define the
functional consequences of the Mendelian mutations that Dr. Holland has identified and how those differences
permit DCM to occur. A second aim is to analyze gene expression of peripheral blood mononuclear cells of
patients with DCM not associated with Mendelian mutations in comparison to persons who control coccidioidal
infection without becoming ill. Such comparisons may identify dysregulated patterns of response and suggest
which putatively deleterious variants in such patients might be responsible. A third aim is to genetically
introduce Mendelian mutations associated with human DCM (such as one found by Dr. Holland in STAT4) into
a mouse strain normally resistant to coccidioidal dissemination to determine if such mutations result in
increased DCM. If so, we can also discover whether it is possible to prevent DCM in the transfected mice by
immunization. The murine studies will use containment facilities available at the UA and not currently available
at the NIH. As a result of this work, it may be possible to identify persons who, if infected, will develop DCM.
Also, our findings may suggest new approaches to therapy or preventative vaccines.

## Key facts

- **NIH application ID:** 9884535
- **Project number:** 5U01AI122275-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** JOHN N GALGIANI
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,465
- **Award type:** 5
- **Project period:** 2017-03-21 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884535

## Citation

> US National Institutes of Health, RePORTER application 9884535, Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis (5U01AI122275-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884535. Licensed CC0.

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