Faculty and Research
Heitman Lab Members
340 CARL Building
Box 3546 DUMC
Durham, N.C. 27710
I have been a faculty member in the Department of Biology at the University of Iowa since 1987. My work there focuses on environmental stress sensing, in particular, signal transduction and modulation of gene expression in response to osmotic, oxidative and wall stress. I have also dabbled in other areas including Drosophila genome annotation and engineering yeast towards a consolidated model of bioethanol production. Most recently, I’ve been involved in a project to screen microalgae native to Iowa to identify oil-rich species that will be useful for biodiesel production. I spent time in the Heitman lab learning how to work with pathogenic fungi and investigating the role of the Skn7 transcription factor in virulence of Cryptocccus neoformans.
The SLN1 signaling pathway is an example of a “two-component” signal transduction pathway whose prominence in prokaryotes, lower eukaryotes and plants but absence from animals makes it an interesting antifungal and antibacterial drug target. “Two-component” pathways are based on a histidine/aspartate phosphorelay. For example, in S. cerevisiae, the SLN1 histidine kinase undergoes autophosphorylation in response to environmental stress and the phosphoryl group on Sln1 is transferred from histidine to aspartate residues within and between proteins in the pathway. Phosphorylation of specific aspartate residues in the terminal molecules of this pathway, including Skn7, leads to changes in gene expression that allow the organism to survive in a constantly changing environment. Skn7 has been reported to be important for virulence of the pathogenic fungi, C. neoformans and C. glabrata. Because of its established role in the fungal oxidative stress response, it has been assumed that it is this aspect of its function that contributes to the ability of the fungus to survive in the host. However, Skn7 has additional important functions that might also be relevant to virulence. I plan to use a variety of approaches including genetic screens, biochemical assays, as well as in vitro and in vivo pathogenesis models to understand the molecular details of the Skn7 contribution to virulence.
He Xin-Jian; Mulford, KariAn E; and Fassler Jan S
Oxidative stress function of the Saccharomyces cerevisiae Skn7 receiver domain.
Eukaryotic Cell 2009;8(5):768-78.
Fassler Jan S and West Ann H
Genetic and Biochemical Analysis of the SLN1 pathway in Saccharomyces cerevisiae
Methods in Enzymology 2009, in press.
Shankarnarayan Sandhya; Malone Cheryl L; Deschenes Robert J; and Fassler Jan S
Modulation of yeast Sln1 kinase activity by the CCW12 cell wall protein.
The Journal of Biological Chemistry 2008;283(4):1962-73.
He Xin-Jian and Fassler Jan S
Identification of novel Yap1p and Skn7p binding sites involved in the oxidative stress response of Saccharomyces cerevisiae. Molecular Microbiology 2005;58(5):1454-67.
Lu Jade Mei-Yeh; Deschenes, Robert J; and Fassler Jan S
Role for the Ran binding protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 signal transduction.
Eukaryotic Cell 2004;3(6):1544-56.
Lu Jade Mei-Yeh; Deschenes Robert J; and Fassler Jan S
Saccharomyces cerevisiae histidine phosphotransferase Ypd1p shuttles between the nucleus and cytoplasm for SLN1-dependent phosphorylation of Ssk1p and Skn7p.
Eukaryotic Cell 2003;2(6):1304-14.
Ault A D; Fassler Jan S; and Deschenes R J
Altered phosphotransfer in an activated mutant of the Saccharomyces cerevisiae two-component osmosensor Sln1p. Eukaryotic Cell 2002; 1(2):174-80.
Li Sheng; Dean Susan; Li Zhijian; Horecka Joe; Deschenes Robert J; and Fassler Jan S
The eukaryotic two-component histidine kinase Sln1p regulates OCH1 via the transcription factor, Skn7p.
Molecular Biology of the Cell 2002; 13(2):412-24.
Tao Wei; Malone Cheryl L; Ault Addison D; Deschenes Robert J; and Fassler Jan S
A cytoplasmic coiled-coil domain is required for histidine kinase activity of the yeast osmosensor, SLN1.
Molecular Microbiology 2002; 43(2):459-73.
Jiao Kai; Nau John J; Cool Marc; Gray William M; Fassler Jan S; and Malone Robert E
Phylogenetic footprinting reveals multiple regulatory elements involved in control of the meiotic recombination gene, REC102. Yeast (Chichester, England) 2002; 19(2):99-114.
Deschenes R J; Lin H; Ault A D; and Fassler Jan S
Antifungal properties and target evaluation of three putative bacterial histidine kinase inhibitors.
Antimicrobial Agents and Chemotherapy 1999; 43(7):1700-3.
Tao W; Deschenes R J; and Fassler Jan S
Intracellular glycerol levels modulate the activity of Sln1p, a Saccharomyces cerevisiae two-component regulator.
The Journal of Biological Chemistry 1999; 274(1):360-7.
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