Academic Section(s):
Microbiology and Immunology
Education:
Ph.D. University of Iowa
B.S. Drake University
Fellowship:
University of Iowa
Clinical/Research Interests:
Invasive Candidiasis is a leading cause of nosocomial bloodstream infections in the United States. Even with currently available antifungal agents, mortality for systemic candidiasis approaches 40%, and its treatments place a tremendous burden and costs on the U.S. healthcare system. To date, only three different classes of antifungal agents are available: triazoles, echinocandins and polyene (amphotericin B). Of these, the most popular are the triazoles with fluconazole being the most routinely used antifungal drug. Multidrug resistance Candida often exhibits elevated minimum inhibitory concentration (MIC) to both triazoles and echinocandins. This leaves amphotericin B, the oldest and most toxic antifungal therapy, as the last line of viable treatment. This underscores the need for a deeper understanding of Candida drug resistance mechanisms as well as the development of novel antifungal drugs.
The Vu’s lab studies the molecular basis of drug resistance mechanisms in Candida species. Our primary foci have been the applications of modern cellular and molecular genetics technologies to elucidate the genetic, lipidomic, and proteomic networks of drug resistance in Candida. Current work involves investigating how Candida responds to antifungal stresses, the activation mechanisms of key regulators in drug resistance, and mechanisms underlying mutant alleles existing in drug resistance clinical isolates. We have also developed numerous genetic tools to manipulate Candida genome and gene regulation, and functional reporter constructs for inhibitor screening and novel therapeutic strategy development. Ongoing projects include:
- Functional and transcriptome analyses of protein kinases in Candida glabrata antifungal drug resistance: There is a significant gap in knowledge concerning the importance of protein kinases (PKs) in drug resistance mechanisms of the human pathogen Candida glabrata. Our long-term goal is to identify key kinases in drug resistance and exploit them for novel drug development. We will construct a C. glabrata PK deletion mutant library, systemically screen mutants in the library for their roles in antifungal drug resistance, analyze their regulation networks, and finally examine their functions in C. glabrata drug resistance clinical isolates.
- Upc2A: A global regulator and an essential factor of Candida glabrata hypoxic metabolism: Maintenance of cellular fitness under hypoxic growth is important for the pathogenesis of C. glabrata, since the conditions mimic the infection environments inside the host. However, transcriptional and cellular responses of C. glabrata shifting from normoxic respiratory (20% ≤ O2) to hypoxic metabolism (1% < O2 < 20%) and the effect of triazole drugs on C. glabrata under hypoxic growth have remained unexplored. To elucidate this, we will acquire an understanding of C. glabrata transcriptional program under hypoxic conditions, including the genes that are directly regulated by Upc2A, Upc2A downstream targets that are essential for C. glabrata hypoxic fitness, and protein interaction partners that require for its hypoxic function.