David R. Andes, MD

Portrait of David R. Andes, MD
Associate Professor
Medicine
Address: 
4476 MSB
1550 Linden Drive
Madison, WI 53706
Telephone: 
(608) 263-1545
Focus Groups: 
Immunology/Immunopathology
Education: 
MD, University of Missouri
Residency/Fellowship, Medicine and Infectious Diseases, University of Wisconsin
Postdoctoral research, University of Wisconsin
Research Summary: 
Antimicrobial resistance development and therapy, Fungal pathogenesis, Candida biofilm pathogenesis and resistance, preclinical anti-infective drug development
Research Detail: 

The focus of research in the Andes Lab involves identification of strategies to combat antimicrobial (especially antifungal) drug resistance. Study approaches include defining the molecular basis for drug resistance, drug target identification and development, pharmacodynamic investigation, and clinical trial study of fungal diagnosis, resistance epidemiology, and therapy.

Fungal Biofilm Resistance: We are interested in the mechanisms underlying the resistance of Candida biofilms to antifungal drugs and the immune system. Studies in the laboratory have identified both a drug sequestering matrix material and the impact of the cell wall integrity pathway as important components for this important phenotype. Ongoing studies seek to define the molecular pathways that control these mechanisms.

In vivo Fungal Biofilms: We have developed several animal models to mimic the most common biofilm infections in humans. We continue to explore the use of these models to study biofilm pathogenesis, drug resistance, host immune response, and biofilm diagnosis. Current models include central venous catheter, denture, and indwelling urinary catheter.

Pharmacodynamics: We seek to understand the relationship between drug exposure and treatment efficacy and failure. Using a variety of in vivo infection models and modeling of antimicrobial pharmacokinetics and pharmacodynamics we define optimal dosing strategies to combat drug resistance therapeutic failures and resistance evolution.

Antimicrobial Drug Development: We utilize in vivo infection models and pharmacodynamic approaches to aid in the early development of lead antibacterial and antifungal compounds. We work closely with several drug discovery groups and biotechnology companies to identify promising molecules and define dosing strategies to bring these drugs to study in clinical trials.

Clinical Mycology and Epidemiology: Our clinical research program provides an opportunity for translation of our laboratory observations to patients. These studies range from fungal epidemiology, to diagnosis and treatment trials.

Selected Publications: 
Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday HD, Tuch BB, Andes DR, Johnson AD. A Recently Evolved Transcriptional Network Controls Biofilm Development in Candida albicans. Cell. 2012 148:126-38.
Andes D, N Safdar, JW Baddley, G Playford, A Reboli, JH Rex, JD Sobel, M Nucci, Pappas, BJ Kullberg. Impact of Treatment Strategy on Outcomes in Patients with Candidemia and Other Forms of Invasive Candidiasis: A Patient Level Analysis of Randomized Trials. Clin Infect Dis 2012 Apr;54(8):1110-1122. Epub 2012 Mar 12. Editors Choice
Finkel JS, Xu W, Huang D, Hill E, Desai JV, Nett JE, Taff H, Norice CT, Andes DR, Lanni F, Mitchell AP. Portrait of Candida albicans adherence regulators. PLoS Pathog 2012 Feb;8(2):e1002525. Epub 2012 Feb 16.
Nett JE, Marchillo K, Andes DR. Modeling of fungal biofilms using a rat central vein catheter. Methods Mol Biol. 2012;845:547-56.
Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H, Cain MT, Hamaker J, Mitchell AP, Andes DR A Candida Biofilm-Induced Pathway for Matrix Glucan Delivery: Implications for Drug Resistance. PLoS Pathogens 2012
Andes D, Ambrose PG, Hammel JP, Van Wart SA, Iyer V, Reynolds DK, Buell DN, Kovanda LL, Bhavnani SM. Use of Pharmacokinetic-Pharmacodynamic Analyses to Optimize Therapy with the Systemic Antifungal, Micafungin, for Invasive Candidiasis or Candidemia. Antimicrob Agents Chemother. 2011 May;55(5):2113-21. Epub 2011 Feb 7.
Nett J, Sanchez H, Cain MT, Ross K, Andes D. Interface of Candida albicans Biofilm -Associated Drug Resistance and Cell Wall Integrity Regulation. Eukaryot Cell. 2011 Jun 10. [Epub ahead of print]
Robbins J, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot J, Andes D, Cowen L. Hsp90 Governs Dispersion and Drug Resistance of Fungal Biofilms" PLoS Pathog 2011 Sep;7(9):e1002257. Epub 2011 Sep 8.
Lepak AJ, Marchillo K, VanHecker J, Andes DR. Posaconazole Pharmacodynamic Target Determination against Wild-type and Cyp51 Mutant Isolates of Aspergillus fumigatus in an in vivo Model of Invasive Pulmonary Aspergillosis. In press