SBRI - Research: Scientists

Mission
Dr. White’s program investigates how the pathogenic yeast Candida interacts with the host during colonization and disease, with an emphasis on current therapies and how the yeast develops resistance to those therapies.

Research
Dr. White's research program is focused on pathogenic yeasts including Candida albicans, the causative agent of oral thrush (candidiasis) in HIV-infected patients, in newborns and the elderly and the major cause of vaginal yeast infections in healthy and immune-compromised women.

Specifically, Dr. White's research focuses on the identification and analysis of virulence factors, traits in the yeast that allow it to interact with its human host and to cause disease. His current research efforts are centered on a recent and significant clinical problem, the emergence of drug-resistant Candida. Dr. White has recently identified genetic changes associated with resistance, including mutation and overexpression of the target enzyme and overexpression of several pumps that control the concentration of the drug within the cell. Genetic and molecular techniques are being used to analyze the basic mechanisms that result in gene expression associated with resistance.

Dr. White and other scientists in his laboratory are also interested in the whole-cell response of Candida cells in the presence of antifungal drugs. Recent data suggests that resistance is associated with mating type, and alters hyphal formation. In collaboration with Dr. Kieren Marr at the Fred Hutchinson Cancer Research Center, Dr. White has described the first example of the development of antifungal drug resistance in bone marrow transplant patients. They have demonstrated that resistance in these isolates is inducible, transient, and part of a "heterozygous resistance" phenotype that is currently being characterized.

Accomplishments
*	Identification and/or characterization of several unique stages in the development of resistance, including transient resistance, heterogeneous resistance, trailing, and inducible resistance.
*	Identification of a linkage between Candida drug resistance and Candida mating loci, suggesting a linkage between the Candida sexual cycle and resistance.
*	Characterization of biochemical pathways important for Candida drug resistance that are also important in cholesterol metabolism in humans.
These accomplishments will be useful for:
*	Improved diagnostics. It may be possible to develop molecular tools that would allow the quick and efficient diagnosis of resistance in clinical isolates.
*	Improved prevention of resistance. Given current information, it is possible to make predictions about how to treat patients without the development of resistance.
*	Improved therapies for the treatment of infections that are resistant to drugs.
*	Insights into drug resistance strategies for other fungi.

Dr. White’s research is currently supported by the National Institutes of Health (NIH).