Role of multi-drug resistant Candida auris Hyr1 / Iff-like proteins in virulence and their potential as vaccine targets

MODIFIED PROJECT SUMMARY/ABSTRACT SECTION Candidate: Dr. Shakti Singh is an accomplished immunologist, working as an Investigator at The Lundquist Institute (TLI) and an Assistant Professor at the University of California, Los Angeles (UCLA). He has demonstrated high research productivity throughout his training with over 20 peer-reviewed publications. This K01 application outlines a career development plan to build professional competency and bridge technical gaps in molecular biology, fungal pathogenesis, and vaccinology, with the objective of achieving full research independence. Mentors/Environment: Dr. Singh will be mentored by an interdisciplinary team with complementary expertise in fungal pathogenesis, immunology, advanced vaccine technologies, and animal modeling. This interdisciplinary mentorship is structured to provide high-level technical training in: 1) acquiring specialized expertise in advanced fungal pathogenesis, molecular biology, and vaccinology; 2) developing advanced technical expertise and project management skills; and 3) conducting high-impact biomedical research with rigorous ethical and professional standards. The collaborative research environment and extensive resources and core research facilities available at TLI, Harbor?UCLA Medical Center, and the UCLA provide an optimal setting for advanced training and career development in infectious disease research. Research: Candida auris is an emerging fungal pathogen responsible for life?threatening bloodstream infections in immunocompromised patients, with mortality rates approaching 60%. C. auris readily colonizes healthcare environments, forms multidrug?resistant biofilms on medical devices, and exhibits resistance to all major classes of clinically available antifungal drugs. To address this unmet clinical need and decipher its virulence mechanisms, we have identified three C. auris Hyr1/Iff?like (CAU?HIL) proteins that are conserved across all known clades. Preliminary studies using monoclonal antibodies targeting conserved CAU?HIL epitopes demonstrate partial protection against disseminated C. auris infection. However, the roles of CAU?HIL proteins in virulence and their potential as vaccine/ immunotherapeutic antigens remain poorly defined. We hypothesize that CAU?HIL proteins play critical roles in C. auris pathogenicity and represent superior immune targets compared to antigens derived from other Candida species. Accordingly, this project will (1) investigate the functional role of CAU-HIL proteins in C. auris virulence and (2) evaluate innovative CAU?HIL?based immune strategies using clinically relevant in vivo infection models.