About
Assistant Professor
Department of Medicine
Lundquist/Harbor-UCLA
Project title: Targeting the regulatory mechanism of hyphae to lateral yeast growth as a novel therapeutic approach against candidiasis
Project Description:
A single species Candida albicans, causes half of all invasive fungal infections in humans. C. albicans hyphae produce yeast cells from their lateral septal regions, coined as “lateral yeasts”. These lateral yeasts are always found with hyphae at the site of active infection, are the major cells that re- enter the bloodstream and establish distal foci of infection. We identified the first regulator of hyphae-to-lateral yeast growth, PES1, and have shown that depleting PES1 in vivo can abrogate disseminated candidiasis as well as biofilm-associated candidemia. Here, using protein biochemistry assays, we propose to delineate how signaling through Ras-PKA regulates Pes1. We will identify other cognate regulators that interact with Pes1 to control lateral yeast growth, and use this information to discover novel compounds that can interrupt hyphae to lateral yeast growth and disseminated candidiasis. Ultimately, better outcomes for patients with indwelling medical devices is the goal of this application.