Department of Medicine
University of Wisconsin
1685 HIGHLAND AVE
MADISON, WI 53705-2281
Chief, Division of Infectious Disease
General Infectious Diseases
Transplant Infectious Diseases
Antimicrobial Pharmacokinetics and Pharmacodynamics
The overriding themes of our research programs are  to advance our understanding of antibacterial and antifungal activity and drug resistance, and  to identify new antimicrobial drug treatment strategies and drug targets.
These studies help determine the optimal therapies used to treat infections due to drug-resistant bacteria and fungi. These studies also identify strategies to prevent the development and emergence of drug-resistance.
Currently we are most actively examining azole resistance in Candida albicans, multi-drug resistance in S. pneumoniae, and ESBL producing gram-negative bacteria
Antimicrobial Pharmacodynamics, Drug Resistance, Molecular Mycology, and Infection Models
These studies are designed to utilize antifungal pharmacodynamics to understand the development of drug resistance. Using a combination of transcript profiling techniques (real time PCR, oligonucleotide arrays, and SAGE), preliminary studies have been successful in describing the relationship between in vitro triazole pharmacodynamics and the emergence of drug resistance. At present, we are developing methodologies to measure fungal transcripts directly from animal infection models. The majority of current gene expression investigations utilize in vitro conditions. We theorize that transcript profiles of these pathogens sampled directly from animal models will more closely represent disease state expression in humans. The three disease state models currently under study include: disseminated candidiasis, an in vivo Candida spp. biofilm model, and an aerosolized Aspergillus spp. pneumonia model.
We plan to utilize these models to study chemogenomics or the global response of fungal cells at the site of infection to antifungal compounds. Results from these studies will help us better understand the mode-of-action of current drugs and those under development and may identify ways to potentiate drug activity through manipulation of antifungal dosing or use of drugs in combination.
Animal Infection Models
We serve as a resource for numerous collaborators to develop animal infection models. These models provide a useful phenotypic screen for gene disruption studies to identify virulence determinants in various pathogens. These animal infection models are also useful for early testing of novel antiinfective compounds.
Our clinical research unit is active in both epidemiologic and treatment studies in collaboration with the NIH Bacterial and Mycoses Study Group and the Centers for Disease Control. Current research projects include surveillance of invasive fungal infections in organ transplant recipients, novel therapies of invasive aspergillosis, and the pathogenesis of Candida line-related infections.
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