University of Washington School of Public Health and Community Medicine Pathobiology Associate ProfessorAppointed: 2001 Seattle Biomedical Research Institute Full MemberAppointed: 2003 |  |
QualificationsPh.D., University of Michigan, Cellular and Molecular Biology, 1984. B.S., Cornell University, Genetics and Biochemistry, 1978. Expertise and Research InterestsMy research interests center on the molecular mechanisms that contribute to virulence in pathogenic fungi. Currently we are investigating the pathogenic yeast, Candida albicans, which is the causative agent of oral candidiasis, the earliest and most frequent infection associated with immune compromised HIV-infected individuals. Our focus is on resistance to antifungal drugs in Candida - a rapidly emerging problem in the HIV-infected population and a problem that is spreading to other immune compromised populations. We have identified several mechanisms of resistance including modification of the target enzyme and overexpression of the target enzyme and various efflux pumps. Other virulence factors of interest include secreated aspartyl proteinases that supress immune function, molecules involved in the adhesion and invasion of Candida to the oral mucosa and signal transduction molecules that allow the cell to vary its repertoire of virulence factors.
Other ExpertiseMolecular parasitology, molecular biology of ciliates
Future ResearchCryptococcus, Aspergillus, Trichophyton rubrum (athlete's foot)
Industrial RelevanceMy current work is directly related to the development of new and improved antifungals/antibiotics. My research involves the study of how a fungal cell (susceptible or resistant) responds to antifungal drugs in vitro and in vivo.
KeywordsCOS Keywords:Drug Resistance, Fungal Diseases, HIV, Molecular Cellular Entities, Pathobiology.Additional Terms:Antifungal Drugs, Candida Albicans, Drug Resistance, HIV Infection, Parasitic Protozoa, Pathogenic Fungi, Secreted Aspartyl Proteinases.MembershipsAmerican Association for the Advancement of Science American Society for Microbiology International Society for Human and Animal Mycology Medical Mycology Society of America Previous Positions2000-2003, Associate Member,
Seattle Biomedical Research Institute
1999, Senior Scientist,
Seattle Biomedical Research Institute
1996-1999, Staff Scientist,
Seattle Biomedical Research Institute
1996-2001, Assistant Professor,
University of Washington
1994-1995, Assistant Research Molecular Biologist II,
University of California, San Francisco
1991-1994, Assistant Research Molecular Biologist I,
University of California, San Francisco
1990-1991, Postgraduate Researcher,
University of California, San Francisco,
Dr. Nina Agabian's Laboratory
1989-1990, Postdoctoral Fellow,
University of California, San Francisco,
Dr. Nina Agabian's Laboratory
1988-1989, Postdoctoral Fellow,
University of California, San Francisco,
Dr. C.C. Wang's Laboratory
1985-1987, Postdoctoral Fellow,
Netherlands Cancer Institute,
Dr. Piet Borst's Laboratory
Funding Received- Murdock Charitable Trust:
New Investigator,
Jul 1997
to Jun 1999.
- Burroughs Wellcome:
New Investigator in Pathogenic Fungi,
Jul 1997
to Jun 2000.
- National Institutes of Health (NIH):
,
to Sep 2002.
Publications- Song JL, Lyons CN, Holleman S, Oliver BG, White TC, Antifungal activity of fluconazole in combination with lovastatin and
their effects on gene expression in the ergosterol and prenylation
pathways in Candida albicans, Medical Mycology : Official Publication of the International Society for Human and Animal Mycology., 41(5), 417-25, October 2003
 - Song JL, White TC, RAM2: an essential gene in the prenylation pathway of Candida albicans, Microbiology (reading, England), 149(Pt 1), 249-59, January 2003
 - Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA, Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1:
high-throughput SNP assays and association with Candida carriage in type I
diabetics and nondiabetic controls, Journal of Clinical Microbiology, 41(1), 90-6, January 2003
 - Starr JR, White TC, Leroux BG, Luis HS, Bernardo M, Leitao J, Roberts MC, Persistence of oral Candida albicans carriage in healthy Portuguese
schoolchildren followed for 3 years, Oral Microbiology and Immunology, 17(5), 304-10, October 2002
 - White TC, Holleman S, Dy F, Mirels LF, Stevens DA, Resistance mechanisms in clinical isolates of Candida albicans, Antimicrobial Agents and Chemotherapy, 46(6), 1704-13, June 2002
 - Rustad TR, Stevens DA, Pfaller MA, White TC, Homozygosity at the Candida albicans MTL locus associated with azole
resistance, Microbiology (reading, England), 148(Pt 4), 1061-72, April 2002
 - Harry, J.B., Song, J.L. Lyons, C.N. and White, T.C., Transcription initiation of genes associated with resistance in Candida albicans, Medical Mycology, 40, 73-81, 2002
- Marr KA, Lyons CN, Ha K, Rustad TR, White TC, Inducible azole resistance associated with a heterogeneous phenotype in Candida albicans, Antimicrobial Agents and Chemotherapy, 45(1), 52-9, Jan 2001
 - White TC, Therapeutic failure and possible involvement of drug resistance: known causes of systemic antimycotic treatment failure, Cutis, 67(4), S38-41, 2001
- Lyons CN, White TC, Transcriptional analyses of antifungal drug resistance in Candida albicans, Antimicrobial Agents and Chemotherapy, 44(9), 2296-303, September 2000
 - Lamb DC, Kelly DE, White TC, Kelly SL, The R467K amino acid substitution in Candida albicans sterol 14alpha-demethylase causes drug resistance through reduced affinity, Antimicrobial Agents and Chemotherapy, 44(1), 63-7, Jan 2000
 - Marr KA, Seidel K, White TC, Bowden RA, Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole, Journal of Infectious Diseases, 181(1), 309-16, Jan 2000
 - Fung-Tomc JC, White TC, Minassian B, Huczko E, Bonner DP, In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole, Diagnostic Microbiology and Infectious Disease, 35(2), 163-7, October 1999
 - Marr KA, Rustad TR, Rex JH, White TC, The trailing end point phenotype in antifungal susceptibility testing is pH dependent, Antimicrobial Agents and Chemotherapy, 43(6), 1383-6, June 1999
 - Naglik JR, Newport G, White TC, Fernandes-Naglik LL, Greenspan JS, Greenspan D, Sweet SP, Challacombe SJ, Agabian N, In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis, Infection and Immunity, 67(5), 2482-90, May 1999
 - Ha KC, White TC, Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans, Antimicrobial Agents and Chemotherapy, 43(4), 763-8, April 1999
 - Buckner FS, Wilson AJ, White TC, Van Voorhis WC, Induction of resistance to azole drugs in Trypanosoma cruzi, Antimicrobial Agents and Chemotherapy, 42(12), 3245-50, December 1998
 - Lopez-Ribot JL, McAtee RK, Lee LN, Kirkpatrick WR, White TC, Sanglard D, Patterson TF, Distinct patterns of gene expression associated with development of fluconazole resistance in serial candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal ca, Antimicrobial Agents and Chemotherapy, 42(11), 2932-7, November 1998
 - Marr KA, Lyons CN, Rustad T, Bowden RA, White TC, Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR, Antimicrobial Agents and Chemotherapy, 42(10), 2584-9, October 1998
 - van Burik JA, Schreckhise RW, White TC, Bowden RA, Myerson D, Comparison of six extraction techniques for isolation of DNA from filamentous fungi, Medical Mycology, 36(5), 299-303, October 1998
 - White, T.C., Marr, K.A. and Bowden, R.A., Clinical, Cellular and Molecular Factors that contribute to antifungal drug resistance., Clinical Microbiology Reviews, 11(2), 382-402, April 1998
- White TC, Marr KA, Bowden RA, Clinical, cellular, and molecular factors that contribute to antifungal drug resistance., Clinical Microbiology Reviews, 11(2), 382-402, 1998
 - Marr K A, White T C, van Burik J A, Bowden R A, Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantation., Clinical Infectious Diseases, 25(4), 908-10, October 1997
 - White T C, The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14alpha demethylase in Candida albicans., Antimicrobial Agents and Chemotherapy, 41(7), 1488-94, July 1997
 - White T C, Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus., Antimicrobial Agents and Chemotherapy, 41(7), 1482-7, July 1997
 - White TC, Pfaller MA, Rinaldi MG, Smith J, Redding SW, Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient., Oral Dis, 3 Suppl 1, S102-9, 1997
 - Kohler GA, White TC, Agabian N, Overexpression of a cloned IMP dehydrogenase gene of Candida albicans confers resistance to the specific inhibitor mycophenolic acid, Journal of Bacteriology, 179(7), 2331-8, April 1997
 - White, T.C., Antifungal drug resistance in Candida albicans, ASM News, 63(8), 427-433, 1997
- White TC, Agabian N, Candida albicans secreted aspartyl proteinases: isoenzyme pattern is determined by cell type, and levels are determined by environmental factors, Journal of Bacteriology, 177(18), 5215-21, September 1995
 - White TC, Andrews LE, Maltby D, Agabian N, The 'universal' leucine codon CTG in the secreted aspartyl proteinase 1 (SAP1) gene of Candida albicans encodes a serine in vivo, Journal of Bacteriology, 177(10), 2953-5, May 1995
 - Agabian N, Odds FC, Poulain D, Soll DR, White TC, Pathogenesis of invasive candidiasis, Journal of Medical and Veterinary Mycology, 32 Suppl 1, 229-37, 1994

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