Aaron P. Mitchell

Professor

Education

Ph.D., Massachusetts Institute of Technology
Postdoctoral Appointment, Department of Biochemistry and Biophysics, University of California at San Francisco

Research

Our interests center on fungal environmental response mechanisms. Our main focus is Candida albicans, the major invasive fungal pathogen of humans. C. albicans causes an array of infections in both immunocompetent and immunocompromised hosts, and our goal is to understand and ultimately combat virulence mechanisms. We also work with the yeast Saccharomyces cerevisiae, which offers unparalleled genetic and post-genomic resources. S. cerevisiae serves as an outstanding model for C. albicans and a system for analysis of basic biological questions.

Our starting point for studies of C. albicans has been the creation and analysis of a library of insertion mutants. The methodology has been slightly involved because C. albicans is a diploid organism that lacks a complete sexual cycle. These insertion mutants have allowed us to define genes that govern key biological processes that are relevant to infection, including biofilm formation, endothelial and epithelial cell interaction, antifungal drug responses, and pH response mechanisms.

We then move from gene discovery to mechanistic inquiry. This effort is challenging because there are many applicable analytical paradigms, but also an incredible amount of fun because one often has to connect some new dots! Our studies have defined new biofilm regulatory pathways that govern adherence and extracellular matrix production, new cell wall damage-response mechanisms that rely upon novel C. albicans-specific components as well as the rewiring of components shared with S. cerevisiae, and have connected a pH-response pathway to conserved endocytic pathways and cell wall modifications that govern pathogen-host interaction.

All TIGR sequences 08_15_05-fa part1.doc
All TIGR sequences 08_15_05-fa part2.doc
All TIGR sequences 08_15_05-fa part3.doc
All TIGR sequences 08_15_05-fa part4.doc
All TIGR sequences 08_15_05-fa part5.doc
TIGR GeneMap.xls
Supplemental Data S2.avi

Publications

Finkel JS and Mitchell AP. Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9, 109-118, 2011.

Dwivedi P, Thompson A, Xie Z, Kashleva H, Ganguly S, Mitchell AP and Dongari-Bagtzoglou A. Role of bcr1-activated genes hwp1 and hyr1 in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One 6, e16218, 2011.

Dagley MJ, Gentle IE, Beilharz TH, Pettolino FA, Djordjevic JT, Lo TL, Uwamahoro N, Rupasinghe T, Tull DL, McConville M, et al. Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the post-transcriptional regulator Ccr4-Pop2. Molecular Microbiology 79, 968-989, 2011.

Argimon S, Fanning S, Blankenship JR and Mitchell AP. Interaction between the Candida albicans High-Osmolarity Glycerol (HOG) Pathway and the Response to Human {beta}-defensins 2 and 3. Eukaryot Cell. 2011 Feb;10(2):272-5. Epub 2010 Dec 3.

Blankenship JR, Fanning S, Hamaker JJ and Mitchell AP. An extensive circuitry for cell wall regulation in Candida albicans. PLoS Pathog 6:e1000752, 2010.

Boysen JH, Subramanian S and Mitchell AP. Intervention of Bro1 in pH-responsive Rim20 localization in Saccharomyces cerevisiae. Eukaryot Cell 9:532-8, 2010.

Fanning S and Mitchell AP. The Fungal Pathogen Candida albicans. In K. A. Borkovich and D. J. Ebbole (ed.), Cellular and Molecular Biology of Filamentous Fungi. ASM Press, Washington, DC, 2010.

Luo G, Ibrahim AS, Spellberg B, Nobile CJ, Mitchell AP and Fu Y. Candida albicans Hyr1p confers resistance to neutrophil killing and is a potential vaccine target. J Infect Dis 201:1718-28, 2010.

Boysen JH, Fanning S, Newberg J, Murphy RF and Mitchell AP. Detection of protein-protein interactions through vesicle targeting. Genetics 182:33-9, 2009.

Nobile CJ, Nett JE, Hernday AD, Homann OR, Deneault JS, Nantel A, Andes DR, Johnson AD and Mitchell AP. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol 7:e1000133, 2009.

Park H, Liu Y, Solis N, Spotkov J, Hamaker J, Blankenship JR, Yeaman MR, Mitchell AP, Liu H and Filler SG. Transcriptional responses of candida albicans to epithelial and endothelial cells. Eukaryot Cell 8:1498-510, 2009.

Chamilos G, Nobile CJ, Bruno VM, Lewis RE, Mitchell AP and Kontoyiannis DP. Candida albicans Cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models. J Infect Dis 200:152-7, 2009.

Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR and Mitchell AP. Complementary adhesin function in C. albicans biofilm formation. Curr Biol 18:1017-24, 2008.

Nobile CJ, Solis N, Myers CL, Fay AJ, Deneault JS, Nantel A, Mitchell AP and Filler SG. Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell Microbiol 10:2180-96, 2008.

Rauceo JM, Blankenship JR, Fanning S, Hamaker JJ, Deneault JS, Smith FJ, Nantel A and Mitchell AP. Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1. Mol Biol Cell 19:2741-51, 2008.

Virtual Tour

Watch Dr. Mitchell discuss the research completed in his laboratory and more.