Dr. Theodore White has been working for the last 20 years to understand the mechanisms of drug resistance in pathogenic fungi. He was the first to characterize point mutations in the target enzyme for azole drugs in Candida albicans and he was one of the first to describe the contribution of efflux pumps to azole resistance in Candida albicans. He was the first to describe the process by which a point mutation in one allele of the target enzyme gene can be copied by gene conversion or homologous recombination to the other allele so that both alleles then contain the resistant mutation, and that with this process, there is a general loss of allelic variation in the gene region. He has extensively characterized a series of 17 clinical isolates from one patient that has provided a wide range of observations on how resistance develops and manifests clinically in a patient. As the general mechanisms of resistance were defined, he then went on to characterize the transcriptional regulation of these mechanisms. He identified and characterized the transcription factor that regulates the target gene and other genes in the sterol biosynthesis pathway. Most recently, he has definitely shown that azole drugs enter the cell via facilitated diffusion rather than passive transport, contrary to widely held beliefs. He and his collaborators also sequenced the genomes of several fungi that cause athlete’s foot, and studied the interaction of those fungi with the host and the immune system. These recent observations have tremendous implications for drug development of azoles and other antifungal compounds. Dr. White’s publications repeatedly move the field of drug response and drug resistance in pathogenic fungi into new and exciting fields.
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