U19AI166059

Host Immunogenetics and Fungal Virulence Mechanisms in Coccidioidomycosis

There is a broad heterogeneity of clinical outcomes after infection with Coccidioides (Cocci), ranging from asymptomatic infection to mild pulmonary disease ("Valley Fever") to a life-threatening, invasive disease called Disseminated Coccidioidomycosis (DCM). 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 why they do so. With nearly 10,000 reported cases of Valley Fever and 200 cases of DCM yearly in California, our state alone spends approximately $1 billion yearly on coccidioidomycosis. Thus, there is an urgent need to better understand DCM to enable better prevention, diagnostics, prognostics, and treatments.

Our team's long-term goal is to study the intersection between the virulence programs of Coccidioides spp that maliciously exploit defective immunity, and the dysregulation of genetic and immunological programs of innate and adaptive immunity that allow for severe disease to take hold. Our program will bring together a cohesive and multi-disciplinary team of immunologists, geneticists, computational biologists, fungal microbiologists, and clinicians. Combining deep expertise with synergistic goals will enable breakthroughs.

Our consortium includes four projects and three supporting cores:

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.

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.

Our program includes an Administrative Core (Core A) that facilitates communications between investigators, organizes meetings and finances, and runs the developmental research program. We also propose a unified Clinical Samples Core (Core B) comprising two of the largest coccidioidomycosis clinics in California, and a Model Organisms Core (Core C) that will carry out all experiments requiring BSL3 safety measures. These cores together empower the proposed projects by providing common reagents, human samples, tools, and expertise.

Our proposed investigations have the potential to transform our understanding of invasive fungal infections and will restore hope for patients through new approaches to prevent, diagnose, and treat DCM.

Los Angeles University Of California

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Los Angeles, California 90095 United States

Single Zip Code

Coccidioidomycosis Collaborative Research Centers (U19 Clinical Trial Not Allowed) (RFA-AI-20-056)

Amendment Since initial award the total obligations have increased 295% from $1,698,839 to $6,713,088.