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Principal Investigator: Shakti Singh
Organization: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
Fiscal Year: 2024
Award: $134,800
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <Address><Adhesions><Adhesives><Agglutinins><Alum Adjuvant><Animal Model><Animal Models and Related Studies><Antigenic Determinants><Antigens><Binding><Binding Determinants><Blood Serum><Body Tissues><C albicans><C auris><C. Auris resistance><C. albicans><C. auris><C.albicans><COVID-19 vaccination><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><California><Candida><Candida albicans><Candida auris><Candidiasis><Candidosis><Cardiac><Cas nuclease technology><Categories><Catheters><Cell Body><Cell Surface Antigens><Cell Surface Proteins><Cell Wall><Cells><Centers for Disease Control><Centers for Disease Control and Prevention><Centers for Disease Control and Prevention (U.S.)><Clinical><Clinical Treatment Moab><Clinical Trials><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Codon><Codon Nucleotides><Coupled><Data><Death Rate><Devices><Disseminated candidiasis><Disseminated candidosis><Dose><Drugs><Encapsulated><Environment><Epitopes><Ethics><Exhibits><Faculty><Family><Gene Transcription><Genes><Genetic Transcription><Goals><Hematogenous><Human><Hyphae><Immune><Immune response><Immunes><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic Surface Markers><Immunological Surface Markers><Immunological response><Immunologist><Immunology><Immunosuppressed Host><In Vitro><Infection><Invaded><Investigators><Leadership><Life><Los Angeles><MDR organism><MDR pathogen><Medical Device><Medical center><Medication><Mentors><Messenger RNA><Mice><Mice Mammals><Microbial Biofilms><Modern Man><Modification><Molecular Interaction><Monilia><Moniliasis><Monoclonal Antibodies><Multi-Drug Resistance><Multidrug Resistance><Multiple Drug Resistance><Multiple Drug Resistant><Murine><Mus><N-terminal><NH2-terminal><Nucleosides><Ortholog><Orthologous Gene><Pathogenesis><Patients><Phagocytes><Phagocytic Cell><Pharmaceutical Preparations><Phase><Plasmid Cloning Vector><Plasmid Vector><Plasmids><Position><Positioning Attribute><Postdoc><Postdoctoral Fellow><Preventive><Productivity><Proteins><Public Health><Publishing><RNA Expression><RNA vaccine><RNA-based vaccine><Recombinants><Reporting><Research><Research Associate><Research Personnel><Research Resources><Researchers><Resistance><Resistance to Multi-drug><Resistance to Multidrug><Resistance to Multiple Drug><Resistant to Multiple Drug><Resistant to multi-drug><Resistant to multidrug><Resources><Role><SARS-CoV-2 vaccination><Scientist><Scourge><Sepsis><Serum><Severe acute respiratory syndrome coronavirus 2 vaccination><Shunt><Shunt Device><Skin><Skin colonization><Stents><Structure><Surface><Surface Antigens><Systemic candida><Systemic candida infections><Systemic candidiasis><Tail><Technology><Testing><Therapeutic Fungicides><Tissues><Training><Transcription><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><Universities><Vaccination><Vaccine Antigen><Vaccines><Venous><Virulence><Vulvovaginal Candidiasis><Vulvovaginal Moniliasis><World Health Organization><Yeasts><alum><aluminum sulfate><amebocyte><anti-fungal><anti-fungal agents><anti-fungal drug><biofilm><blood infection><bloodstream infection><career development><clinical relevance><clinically relevant><combat><coronavirus disease 2019 vaccination><cost effective><develop a vaccine><develop drug resistance><develop vaccines><development of a vaccine><drug resistance development><drug/agent><efficacy testing><environment enrichment><environment enrichment for laboratory animals><environmental enrichment><environmental enrichment for laboratory animals><ethical><experience><fungus><global health><health care settings><health care-associated infections><healthcare settings><healthcare-associated infections><high risk><host response><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><immunosuppressed patient><improved><in silico><in vivo><infection risk><innovate><innovation><innovative><lipid based nanoparticle><lipid nanoparticle><mAbs><mRNA><mRNA lipid nano particle vaccine><mRNA vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><mRNA-based vaccine><model of animal><monoclonal Abs><mortality rate><mortality ratio><mouse model><multi-drug resistant><multi-drug resistant organism><multi-drug resistant pathogen><multidrug resistant><multidrug resistant organism><multidrug resistant pathogen><multiple drug resistant organism><multiple drug resistant pathogen><murine model><mutant><new vaccines><next generation vaccines><novel vaccines><pathogen><plasmid DNA><post-doc><post-doctoral><post-doctoral trainee><posttranscriptional><prevent><preventing><professor><promoter><promotor><protective efficacy><research associates><resistance development in C. Auris><resistance in Candida auris><resistant><resistant Candida auris><responsible research conduct><shunts><skills><social role><success><therapeutic target><therapeutic vaccine><trait><treatment vaccines><urinary><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine candidate><vaccine development><vaccine for the treatment><vaccine for treatment><vaccine strategy><vulvovaginal yeast infection>