A team led by UCLA researchers will receive a multi-million dollar grant to study why some people suffer from a devastating fungal infection called Valley Fever, while others suffer seemingly no impact from the disease. Dr. Manish Butte of UCLA will lead a group receiving $8.4 million over five years from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to establish one of three Coccidioidomycosis Collaborative Research Centers. Dr. Butte is the E. Richard Stiehm Endowed Chair, professor and chief of the division of immunology, allergy and rheumatology in the department of pediatrics, and will lead a group of researchers from UCLA and UC San Diego. Patient samples for their project will come from collaborators at the UC Davis Center for Valley Fever and the Valley Fever Institute of Kern Medical Center.
The Coccidioides (“cocci’) fungi that cause Valley Fever grow in the soils of California and the desert Southwest, and range down through Central America all the way down to Argentina, where it was first identified in the late 1800s. The majority of people who are infected have no to mild symptoms and recover with no treatment or with antifungal medication, but for reasons unknown some experience a life-threatening, invasive disease called disseminated coccidioidomycosis (DCM) that ravages the body.
“Everyone in the endemic areas is susceptible to this infection, but we have almost no ability to predict who will develop disseminated disease and lack an understanding of what part of their immune response fails to control the infection. With nearly 10,000 reported cases of Valley fever and 200 cases of DCM yearly in California, our state alone spends approximately $1 billion per year on coccidioidomycosis,” said Butte. “There is an urgent need to better understand DCM to enable better prevention, diagnostics, prognostics and treatments.”
The team led by Dr. Butte will study the intersection between virulent coccidioides that takes advantage of compromised immunity and the genetic risk factors that allow severe disease to infect and take hold.
The team will work in parallel with awardees from UC San Francisco and the University of Texas, San Antonio, to transform our understanding of this invasive fungal infection, restoring hope for patients through new approaches to prevent, diagnose and treat DCM.
The NIH grant supports four research projects and three supporting cores at UCLA and UCSD:
- Project 1 addresses the innate immune responses to cocci infection that go awry in the first stages of cocci infection.
- Project 2 addresses the adaptive immune responses to cocci infection that go awry in protecting the host from disseminated disease and that are needed for long-term protection.
- Project 3 addresses the genomic basis of cocci disease, from common variants that underlie susceptibility due to ancestry to rare variants that disable host defenses.
- Project 4 addresses the contributions of fungal virulence factors in enabling the organisms to evade host immune defenses in some individuals.
This joint project arose between UCLA and UCSD because of the long-standing and collaborative relationship Dr. Butte has with his colleague, pediatric immunologist and division chief Dr. Hal Hoffman at UCSD. Other researchers at UCLA working on this project include Dr. Maria Garcia-Lloret, Dr. Valerie Arboleda, Dr. Bogdan Pasaniuc, Dr. Harold Pimentel and Dr. Paul Krogstad. Dr. Hal Hoffman from UCSD serves as a co-PI along with colleagues Dr. Joshua Fierer, Dr. Sinem Beyhan, Dr. Theo Kirkland, Dr. Aaron Carlin and Dr. Ben Croker. Infectious diseases experts and faculty collaborators offering their clinical know-how and patient samples include Dr. George R. Thompson from the UC Davis Center for Valley Fever and Dr. Royce Johnson from the Valley Fever Institute at Kern County Medical Center.
The research is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. (Award No. U19AI166059)