NIH grant: A New Model for Valley Fever: Comparative Volatilomics of Coccidioides Infection (1R03AI202025-01)

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NIH grant 1R03AI202025-01: A New Model for Valley Fever: Comparative Volatilomics of Coccidioides Infection
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Emily A Higgins Keppler. Award: $78500.
Start: 2026-08-07T00:00:00.
Project Summary: Coccidioidomycosis (Valley fever) is an emerging fungal pneumonia endemic to the
southwestern United States, caused by Coccidioides immitis and C. posadasii. Unlike most fungal pathogens,
these dimorphic fungi can cause severe disease in otherwise healthy individuals. The incidence of Valley fever
is rising rapidly, with a 142% increase in reported U.S. cases from 2014 to 2019, and its expanding geographic
range is linked to increased desertification. The economic burden exceeds $385 million annually due to delayed
diagnosis and excess medical care. Despite its growing public health importance, the mechanisms driving
variability in disease severity and the molecular signatures of infection remain poorly understood.
Current Coccidioides infection models rely primarily on mice, which provide valuable insights but ethical and
budgetary hurdles reduce the efficacy of this model. These constraints hinder the ability to investigate
pathogenicity variables such as strain, dose, and life-stage transitions in a high-throughput manner. To overcome
these barriers, this project proposes to develop a Galleria mellonella (greater wax moth) infection model as a
scalable, ethical, and cost-effective system for studying Coccidioides infection through volatile metabolomics.
Galleria have recently emerged as a promising model system for Coccidioides. Importantly, VOCs have been
collected from Galleria infected with the bacterial pathogen Pseudomonas aeruginosa, establishing the technical
feasibility of this proposal. Despite this potential, the Coccidioides Galleria volatilome remains unexplored.
The long-term objective of this research is to establish a robust, high-throughput, and ethical infection model for
Valley fever research that accelerates biomarker discovery and diagnostic development. The overall goal of this
R03 proposal is to evaluate the Coccidioides Galleria infection model as a valid platform for infection-associated
volatilomics. We will begin by testing our central hypothesis that Galleria infections recapitulate key volatilome
characteristics observed in murine and in vitro systems, enabling its use as a comparative and translational
model for Valley fever research, through one Specific Aim: 1. Compare the volatile organic compounds of
the Coccidioides Galleria infection model to previously defined murine and in vitro volatilomes. Fungal
burden and targeted and untargeted volatilomics will be used to characterize infection across multiple strains,
enabling comparison with existing murine and in vitro models.
Expected outcomes. Completion of this project will generate the first comprehensive comparison of
Coccidioides volatilomes across invertebrate, mammalian, and in vitro systems. These results will have
significant positive impact as it will establish the Galleria infection model as a low-cost, high-throughput, and
ethically accessible tool for Coccidioides research. By facilitating discovery of breath-based biomarkers for
diagnosis, prognosis, and treatment monitoring, this work directly supports the NIH mission to improve human
health through innovative approaches to prevent, detect, and manage infectious diseases.

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