Ph.D. University of Michigan
In my laboratory, we study fungi that are pathogenic to humans, including Candida albicans (cause of oral, vaginal and systemic fungal diseases) and the Dermatophytes (cause of athlete’s foot and jock itch). We occasionally use other human fungal pathogens as well for comparison purposes.
In Candida albicans, we study the regulation of sterol metabolism. Fungal cells produce ergosterol and mammalian cells produce cholesterol. Both sterols are the major membrane sterol in their respective organisms. We study the sterol biosynthetic pathway and its regulation, with the goal of understanding how fungal cells respond to antifungal drugs that target the pathway. This includes how the fungal cells develop resistance, through modification of the sterol pathway and through over-expression and modification of efflux pumps.
Our recent efforts have demonstrated that azole antifungal drugs enter the cell through an active process, which contradicted previous dogma that the drugs entered passively. We are currently focused on identifying the protein (or other molecule) that is involved in moving azole drugs into fungal cells. This has implications for all fungal diseases, including medical, veterinary and plant pathogens.
In the dermatophytes, we are completing the genome sequences and annotation of five species that exhibit a spectrum of virulence, mating, and host specificity. We are also developing molecular techniques to work with the dermatophytes, including improving the transformation system and using of skin explants and wax moth larvae as models for virulence and pathogenicity.Selected Publications
Hoot SJ, Brown RP, Oliver, BG, White, TC (2010). Two cis-acting elements within the Candida albicans UPC2 promoter are necessary for azole induction and direct binding to Upc2p, resulting in transcriptional autoregulation. Eukaryotic Cell 9: 1354-1362. Article
Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC (2010). Azole antifungal drug import requires a transporter in Candida albicans and other pathogenic fungi. PLoS Pathogens 6: e1001126. Article
Achterman, RR, Smith, AR Oliver BG, White TC (2011) Sequenced dermatophyte strains: growth rate, conidiation, drug susceptibilities, and virulence in an invertebrate model. Fungal Genetics and Biology 48: 335-341. Article
Martinez DA, Oliver BG, Gräser Y, Goldberg JM, Li W, Martinez-Rossi NM, Monod M, Shelest E, Barton RC, Birch E, Brakhage AA, Chen Z, Gurr SJ, Heiman D, Heitman J, Kosti I, Rossi A, Saif S, Samalova M, Saunders CW, Shea T, Summerbell RC, Xu J, Young S, Zeng Q, Birren BW, Cuomo CA, White TC (2012) Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection. mBio 3: e00259-12. Article