Aaron P. Mitchell Professor Ph.D., Massachusetts Institute of Technology Postdoctoral Appointment, Department of Biochemistry and Biophysics, University of California at San Francisco apm1@andrew.cmu.edu 412-268-5844 (Phone) 412-268-7129 (Fax) 741 Mellon Institute Department of Biological Sciences Carnegie Mellon University 4400 Fifth Avenue Pittsburgh, PA 15213

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.

Selected Publications

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. The Journal of infectious diseases 200, 152-157, 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 biology 7, e1000133, 2009.

Boysen JH, Fanning S, Newberg J, Murphy RF and Mitchell AP. Detection of Protein-protein Interactions Through Vesicle Targeting. Genetics 182(1),33-9, 2009.

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, 2180-2196, 2008.

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, 1017-1024, 2008.

Mitchell AP. A VAST staging area for regulatory proteins. Proc Natl Acad Sci USA, 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, 2008.

Chiang LY, Sheppard DC, Bruno VM, Mitchell AP, Edwards JE, Jr., and Filler SG. Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell Microbiol 9, 233-245, 2007.

Nobile CJ and Mitchell AP. Microbial biofilms: e pluribus unum. Curr Biol 17, R349-353, 2007.

Norice CT, Smith FJ, Jr., Solis N, Filler SG, and Mitchell AP. Requirement for Candida albicans Sun41 in biofilm formation and virulence. Eukaryot Cell 6, 2046-2055, 2007.