Role of multi-drug resistant Candida auris Hyr1 / Iff-like proteins in virulence and their potential as vaccine targets - PROJECT SUMMARY:
Candidate’s Career Development: Dr. Shakti Singh, an accomplished immunologist, presently holds the
positions of Investigator and Assistant Professor at The Lundquist Institute (TLI) and the University of
California, Los Angeles (UCLA), respectively. Over the past seven years at TLI, Dr. Singh has exhibited
remarkable productivity, published over 20 research articles, and has ascended from a postdoctoral
trainee to a faculty rank. This application outlines a project leveraging his existing expertise to fill gaps in his
training in the fungal field, with the ultimate goal of achieving full independence.
Mentors/Environment: Dr. Singh will be guided by a diverse team of accomplished scientists with
expertise in Fungal pathogenesis, immunology, vaccine development, animal modeling, and mRNA vaccine
technology. This team is well-positioned to provide hands-on experience and support, Dr. Singh, in
achieving the outlined training goals: 1) filling gaps in research expertise, 2) developing professional and
leadership skills, and 3) conducting research responsibly, ethically, and efficiently. The collaborative and
enriching environment, coupled with the abundant resources at TLI, Harbor-UCLA Medical Center, and
UCLA, offers an optimal setting for comprehensive professional training.
Research: C. auris is a recently discovered Candida species that causes life-threatening bloodstream
infections (BSI) in immunosuppressed patients and has a very high (~60%) mortality rate. C. auris easily
colonizes and spreads in healthcare settings and adheres and forms biofilms on medical devices. The majority
(~88%) of C. auris BSI cases can be attributed to the involvement of catheters and other invasive medical
devices. C. auris infections are hard to treat because C. auris can resist all classes of clinically available
antifungal drugs. Due to these reasons, the World Health Organization and Center for Disease Prevention and
Control (CDC) have categorized C. auris as a “Critical threat” and “Urgent Threat” pathogen, respectively. To
address this urgent public health challenge, we have identified three Hyr1/Iff family (CAU-HIL) proteins that
demonstrate universal presence across all clades of C. auris. Using a monoclonal antibody targeted against
an epitope in the C. albicans Hyr1 protein, conserved in CAU-HIL, we have ascertained these proteins as
potential therapeutic targets. However, CAU-HIL proteins exhibit only ~35% sequence identity with
characterized proteins in other Candida species, and their specific role in C. auris virulence remains
uncharacterized. We hypothesize that these CAU-HIL proteins would be superior vaccine candidates
against C. auris infection compared to C. albicans antigens, simply because of their C. auris origin.
Therefore, we propose to: 1. study the role of HIL proteins in C. auris virulence, 2. Study their potential as a
vaccine against C. auris using an innovative mRNA platform and clinically relevant animal models.
