wiederholdn@uthscsa.edu
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Background
Dr. Nathan Wiederhold joined the Division of Pharmacotherapy as an assistant
professor in the Fall of 2004. He received his B.A. in Biology and his
Pharm.D. from the University of Texas at Austin followed by Pharmacy Practice
and an Infectious Diseases residencies at Barnes-Jewish Hospital in St.
Louis. Upon finishing his clinical training Dr. Wiederhold completed a
research fellowship in Antifungal Pharmacology at the University of Houston
and the University of Texas M.D. Anderson Cancer Center under the supervision
of Russell Lewis, Dimitrios Kontoyiannis, and Randall Prince. His area
of work during this fellowship was studying pharmacokinetic/pharmacodynamic
parameters associated with antifungal efficacy with a primary focus on
the echinocandin class of antifungals against Aspergillus and Candida
species, and the cellular response of these organisms to this class of
agents.
Research Program
Increases in the number of cases of opportunistic fungal infections in immunocompromised patient populations
have occurred over the last two decades. Due to the high morbidity and mortality rates associated with these
infections much attention has recently been focused in this area. Despite recent advances in antifungal
pharmacology and the availability of new agents, favorable response rates to such infections are low. Up-regulation
of expression of various genes involved in encoding essential components of the cell integrity/cell wall maintenance
pathways have been demonstrated in response to cell-wall disrupting agents, hypo-osmotic stress, heat stress, and anionic
detergents. These pathways, and the increased expression of genes encoding proteins important in the cellĂs response
to such stresses, have been found to be conserved in a number of fungi, including S. cerevisiae, C. albicans,
C. neoformans, and P. carinii. My primary research interests lie in the study of responses of various pathogenic
fungi (e.g. Aspergillus & Candida species) to a number of drugs commonly used in patients at risk, including currently
available and investigational antifungal agents as well as other drugs that can influence responses of these organisms
and are often employed in these patient populations. A major focus of my research includes an emphasis on the study
of different cellular pathways in order to better understand how these organisms adapt in hopes of developing more
effective treatment strategies. Also, because of structural similarities between these lower eukaryotes and mammalian
cells resulting in collateral toxicities associated with the use of various antifungal agents, different strategies that
aim to minimize such toxicities will also be investigated.
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