Environmental response pathways are of interest as models for conserved signal transduction pathways and as determinants of virulence among microbial pathogens. Our studies have focused on the mechanisms through which yeast cells sense and respond to changes in external pH. Two pathways that are required for growth of budding yeast Saccharomyces cerevisiae at alkaline pH and whose homologs are required for full virulence of the fungal pathogen Candida albicans: the Rim101p pathway and the MdsSp pathway. Our broad objective is to understand, for each pathway, the specific signal that is recognized, the mechanism of signal transduction, and the target genes and functions that contribute to pathogenicity. Our experimental methods employ mainly genetic and cell biological methods.
Our specific aims are to identify the signal that governs Rim101p pathway activity, to determine the relationship of Mds3p/Pmd1p to transcriptional targets, and to determine the roles of C. albicans Rim101p and MdsSp target genes in virulence. Our work is relevant to public health in providing insight into how an infectious disease agent is able to grow in so many different body sites, and how it damages our cells to cause disease and death.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Pathogenic Eukaryotes Study Section (PTHE)
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Duncan, Rory A
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Carnegie-Mellon University
Schools of Arts and Sciences
United States
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Ichikawa, Yuichi; Morohashi, Nobuyuki; Tomita, Nobuyuki et al. (2016) Sequence-directed nucleosome-depletion is sufficient to activate transcription from a yeast core promoter in vivo. Biochem Biophys Res Commun 476:57-62
O'Meara, Teresa R; Xu, Wenjie; Selvig, Kyla M et al. (2014) The Cryptococcus neoformans Rim101 transcription factor directly regulates genes required for adaptation to the host. Mol Cell Biol 34:673-84
Bishop, Andrew C; Ganguly, Shantanu; Solis, Norma V et al. (2013) Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence. J Biol Chem 288:33939-52
Subramanian, Shoba; Woolford, Carol A; Desai, Jigar V et al. (2012) cis- and trans-acting localization determinants of pH response regulator Rim13 in Saccharomyces cerevisiae. Eukaryot Cell 11:1201-9
Boysen, Jacob H; Subramanian, Shoba; Mitchell, Aaron P (2010) Intervention of Bro1 in pH-responsive Rim20 localization in Saccharomyces cerevisiae. Eukaryot Cell 9:532-8
Boysen, Jacob H; Fanning, Saranna; Newberg, Justin et al. (2009) Detection of protein-protein interactions through vesicle targeting. Genetics 182:33-9
Nobile, Clarissa J; Solis, Norma; Myers, Carter L et al. (2008) Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell Microbiol 10:2180-96
Mitchell, Aaron P (2008) A VAST staging area for regulatory proteins. Proc Natl Acad Sci U S A 105:7111-2
Morohashi, Nobuyuki; Nakajima, Kumiko; Kurihara, Daichi et al. (2007) A nucleosome positioned by alpha2/Mcm1 prevents Hap1 activator binding in vivo. Biochem Biophys Res Commun 364:583-8
Villar, C C; Kashleva, H; Nobile, C J et al. (2007) Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect Immun 75:2126-35

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