Research Interests:
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 cell’s 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 will include 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.

Publications:

• Wiederhold NP, Kontoyiannis DP, Chi J, Prince RA, Tam VH, Lewis RE. Pharmacodynamics of Caspofungin in a Murine Model of Invasive Pulmonary Aspergillosis: Evidence of Concentration-Dependent Activity. Journal of Infectious Diseases 2004; 190: 1464-71.

• Barker KS, Crisp S, Wiederhold NP, Lewis RE, Rogers PD. Genome Wide Expression Profiling Reveals Genes Associated with Amphotericin B and Fluconazole Resistance in Experimentally Induced Antifungal Resistant Isolates of Candida albicans. Journal of Antimicrobial Chemotherapy 2004; 54: 376-85.

• Wiederhold NP, Lewis RE, Kontoyiannis DP. Invasive Aspergillosis in Patients with Hematological Malignancies. Pharmacotherapy, 2003; 23(12): 1592-1610.

• Wiederhold NP, Lewis RE. The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy. Expert Opinion on InvestigationalDrugs 2003; 12 (8): 1313-1333.