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Michael C. Gustin Professor Professor of Biochemistry and Cell Biology e-mail:[email protected] B.A., Johns Hopkins University, 1974 (Biology) Ph.D., Yale University, 1981 (Cell Biology) Primary Department Department of BioSciences Department Affiliations Institute of Biosciences and Bioengineering Research Areas Molecular genetics and biochemistry of signal transduction. Research Statement 2010 A fundamental problem in biology is how cells sense and respond to stimuli such as changes in pressure, osmolarity, or mechanical forces. Most of our research employs the yeast Saccharomyces cerevisiae as a model system for understanding the molecular mechanisms required for sensing and responding to changes in external osmolarity and other stresses. Genetic and biochemical analysis of mutants that fail to grow in high (or low) osmolarity media has allowed us to uncover two stress-activated signaling pathways, the hog and cell intensity pathways, respectively. Both of these pathways contain a unique map kinase cascade. We are currently investigating the mechanism of osmosensing and transcriptional regulation by these pathways plus their role in osmotic stress-induced cell cycle delay. A pathway similar to the yeast hog pathway is found in osteoblasts, mammalian cells not usually exposed to osmotic stress. We are therefore investigating the role of the hog pathway in responses of these cells to mechanical stress. In addition, my research group, in collaboration with Dr. Mikos (Bioengineering, Rice U.), is examining the function of the mammalian hog pathway in mediating activation of bone forming cells by mechanical stress. Selected Publications Abstracts Tchou, G., Smith, P., Zhang, A., Razani, B., Flores, V., and Gustin, M.C. "Transmembrane domains of the osmosensor Sln1 regulate signaling." 2004 Yeast Genetics and Molecular Biology Meeting, July 27, 2004 (2004) Refereed articles Brewster JL, Gustin MC "Hog1: 20 years of discovery and impact." Sci Signal, 7(343) (2014) : re7. doi: 10.1126/scisignal.2005458 Radmaneshfar E, Kaloriti D, Gustin MC, Gow NA, Brown AJ, Grebogi C, Romano MC, Thiel M. "From START to FINISH: the influence of osmotic stress on the cell cycle." PLOS ONE (2013) : e68067. Vu MT, Zhai P, Lee J, Guerra C, Liu S, Gustin MC, and Silberg JJ. "The DNLZ/HEP zinc-binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9." Protein Sci., 21(2) (2012 Feb) : 258-67. Allen, G.I., Christian, J.B., Chiranand, W., Pletcher, S., Gustin, M.C., and Guerra, R. "Chomosomal spatial correlation of gene expression: Analysis and visualization." Bioinformatic (2006) In Press Chiranand, W., McLeod, I., Zhou, H., Lynn, J.J., Vega, L.A., Myers, H., Yates, J.R., 3rd., Lorenz, M.C., and Gustin, M.C. "The CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans." Eukaryotic Cell, 7 (2008) : 268-278. Christian, J.B., Shaw, C., Noyola-Martinez, J., Gustin, M.C., Scott, D.W., and Guerra, R. "Chromosomal spatial correlation of gene expression in Plasmodium falciparum." Methods Microarray Data Analysis, 5 (2007) : 157-171. Guerra, R., Shaw, C., Christian, J.B., Fox, G., Noyola-Martinez, J., Stevens, M., Garg, N., and Gustin, M.C. "Oxidative stress genes in Plasmodium falciparum as indicated by temporal gene expression." Methods Microarray Data Analysis, 5 (2007) : 45-58. Padda, R., Wamsley-Davis, A., Gustin, M.C., Ross, R., Yu, C., and Sheikh-Hamad, D. "MEKK3Mediated signaling to p38 kinase and TonE in hypertonically stressed kidney cells." Am. J. Physiol. Renal. Physiol, 291 (2006) : F874-F881. Christian, J.B., Shaw, C., Noyola-Martinez, J., Gustin, M.C., Scott, D.W., and Guerra, R. "Spatial correlation of expression in P. falciparum." Methods of Microarray Data Analysis (2005) In Press Helmick, R.A., Fletcher, A.E,, Gardner, A.M., Gessner, C.R., Hvitved, A.N., Gustin, M.C. and Gardner, P.R. "Imidazole antibiotics inhibit the nitric oxide dioxygenase function of microbial flavohemoglobins." Antimicrob. Agents Chemother., 49 (2005) : 1837-1843. May, G.S., Xue, T., Kontoyiannis, D.P., and Gustin, M.C. "The mitogen activated protein kinases of Aspergillus fumigatus." Medical Mycology, 43 Suppl 1 (2005) : 583-586. Sheikh-Hamad, D., and Gustin, M.C. "Adaptation to dehydration: osmostress response pathways in mammals and yeast." Amer. J. Physiol., 287 (2004) : F1002-1110. Ullmann, B.D., Myers, H., Chiranand, W., Lazzell, A.L., Zhao, Q., Vega, L., Lopez-Ribot, J., Gardner, P., and Gustin, M.C. "Inducible defense mechanism against nitric oxide in Candida albicans." Eukaryotic Cell, 3 (2004) : 715-723. Huang, X., Huang, Y., Chinnappan, R., Bocchini, C., Gustin, M., and Stern, M. "The Drosophila inebriated-Encoded Neurotransmitter/Osmolyte Transporter: Dual Roles in the Control of Neuronal Excitability and the Osmotic Stress Response." Genetics, 160 (2002) : 561-569. Alexander, M., Tyers, M., Perret, M., Craig, B.M., Fang, K.S., and Gustin, M.C. "Regulation of Cell Cycle Progression by Swe1p and Hog1p Following Hypertonic Stress." Mol. Biol. Cell, 12 (2001) : 53-62. Goldstein, A.S., Juarez, T.M., Helmke, C.D., Gustin, M.C., and Mikos, A.G. "Effect of Convection on Osteoblastic Cell Growth and Function in Biodegradable Foam Scaffolds." Biomaterials, 22 (2001) : 1279-1288. Alonso-Monge, R., Navarro-Garcia, F., Molero, G., Diez-Orejas, R., Gustin, M., Pla, J., Sanchez, M., and Nombela , C. "Role of the Mitogen-activated Protein Kinase Hog1p in Morphogenesis and Virulence of Candida albicans." J. Bacteriology, 181 (1999) : 3058-3068. Davenport, K.D., Williams, K.E., Ullmann, B.D., and Gustin, M.C. "Activation of the Saccharomyces cerevisiae Filamentation/Invasion Pathway by Osmotic Stress in HOG Pathway Mutants." Genetics, 153 (1999) : 1091-1103. Articles Gustin, M.C., Albertyn J., Alexander, M.A., and Davenport, K. "MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae." Microbiol. Mol. Biol. Rev., 62 (1998) : 1264-1300. Presentations Invited Talks "Cells Under Stress: Signals, Pathways and Sensors." Department of Mol. Physiology & Biophysics, Baylor School of Medicine. (May 10, 2005) "Kenan-inspired Changes in the Teaching of Biology in the Introductory Biology Course at Rice University." Kenan Symposium, NTBG/Kampong, Coconut Grove, Florida. (February 5-7, 2005) "Signaling Pathways Activated by Nitric Oxide: A Profusion of Mediators." UK-Texas Bioscience Collaboration "Post Receptor Events in Cell Signalling and Disease", University of Dundee. (September 12-14, 2005) "The Role of Transmembrane Helix Association in Osmosensing by the Sln1 Protein." Gordon Conference on "Mechanotransduction and Gravity Signaling in Biological Systems", (July 2429, 2005) "Biology of Aging." Rice Homecoming and Reunion, Houston, Texas. (November 5, 2004) "Nitric Oxide Signaling in Candida albicans." South Central Medical Mycology Meeting, New Orleans, Louisiana. (October 20-22) "On Aging, Wine, and Friends." Recent Alumni Reception, Rice University, Houston, Texas. (January 15, 2004) Other "Different roles of the HOG pathway in stress responses of yeast." ISOPOW meeting (8th International Symposium on the Properties of Water), Zichron Yaakov, Israel. (Sept 16-21, 2000) Panelist 7th International Conference on the Biology, Chemistry and Therapeutic Application of Nitric Oxide, Edinburgh, Scotland, July 2012 Supervised Theses & Dissertations Lei Tang, Ph.D. A Cell Number-Counting Factor Regulating Group Size in Dictyostelium discoideum. (2002) (Committee Member) Brett Schweers, Ph.D. The Drosophila melanogaster Gene, bemused, Is a New Allele of pumilio: Insights into Understanding the Role of Translational Regulation in the Maintenance of Proper Neuronal Excitability. (2002) (Committee Member) Wafa Elbjeirami, Ph.D. Genetic Modification of Smooth Muscle Cells to Enhance the Performance of Tissue Engineered Vascular Grafts. (2003) (Committee Member) Wonhee Yang, Ph.D. Theoretical and Experimental Studies on a Cell Number Sensing Mechanism. (2003) (Committee Member) Dennis Lee, Ph.D. Plant Responses to Environmental Stimuli: A Screen for Mutants in TCH4 Expression Behavior, and a Full-genome Assessment of Touch and Darkness Inducibility. (2004) (Committee Member) Melanie Monroe-Augustus, Ph.D. Genetic Approaches to Elucidating the Mechanisms of Indole3-Acetic Acid and Indole-3-butyric Acid Function in Arabidopsis thaliana. (2004) (Committee Member) Miles Scotcher, Ph.D. Genetic Factors Affecting the Regulation of Solventogenesis in Clostridium acetobutylicum ATCC 824. (2004) (Committee Member) Veronica Hall-O'Connell, Ph.D. Broad-Complex, a Mediator of Ecdysone Induced Stress Response in Drosophila melanogaster. (2004) (Thesis or Dissertation Director) Rebekah A. Rampey, Ph.D. Genetic Analysis of IAA-Conjugate Sensitivity in Arabidopsis thaliana: Hydrolysis, Transcriptional Regulation, and Metal Homeostasis. (2004) (Committee Member) Beth E. Jackson, Ph.D. Yeast as a Host for Sesquiterpene Production. (2004) (Committee Member) Samuel Campos, Ph.D. Metabolic Biotinylation of the Adenoviral Capsid: Avidin-Based Applications and Studies of Ligand-Targeted Gene Delivery. (2005) (Committee Member) Hongli Zhan, Ph.D. Biophysical Characterization of the Allosteric Transition in Lactose Repressor Protein (LacI). (2005) (Committee Member) Jeff Van Komen, Ph.D. Regulatory Elements of Sso1p and Their Effect on SNARE Mediated Membrane Fusion. (2005) (Committee Member) Gia Fazio, Ph.D. Unveiling Relationships among Triterpene Synthases in Higher Plants Through Enhanced Heterologous Expression in Yeast. (2006) (Committee Member) Angela Noel Hvitved, Ph.D. NO Dioxygenation in Mammalian Hemoglobins and Microbial Flavohemoglobins. (2007) (Committee Member) Diana Dugas, Ph.D. Genetic Analysis of MicroRNA Function in Arabidopsis Development. (2007) (Committee Member) Blair Doneske, Ph.D. Regulation of Neuronal SNARE Complexes by Complexin and Ca++Synaptotagmin. (2007) (Co-Director) Wiriya Chiranand, Ph.D. Regulation of Nitrosative Stress Response in the Fungal Pathogen Candida albicans by CTA4, a DNA-Binding Protein Transcription Factor. (2007) (Thesis or Dissertation Director) Michael Texada, Ph.D. Characterization of the Drosophila Gene ‘yuri gagarin,’ Which Is Required for Mechanosensation and Male Fertility. (2008) (Committee Member) E. Shannon Neeley, Ph.D. Models for the Preprocessing of Reverse Phase Protein Arrays. (2008) (Committee Member) Jed Lynn, Ph.D Anticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicans. (2012) (Thesis or Dissertation Director) Curtis Warren, Ph.D. Evolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Cancer. (2014) (Committee Member) Ye Chen, PhD Multi-strain synthetic biology: Design and construction of genetically controlled micro-ecosystems. (Committee Member) Yasmin Chebaro, PhD Sulfur metabolism of Candida albicans: Adaptation to sulfite and biofilm formation. (Thesis or Dissertation Director) Kathryn R Beaubout, PhD Evolutionary dynamics leading to tigecycline resistance in a hospital strain of Enterococcus faecalis. (Committee Member) Yanmei Huang, Ph.D. A Genetic Study of inebriated, a Drosophila Gene that Plays Dual Roles in the Control of Neuronal Excitability and the Osmotic Stress Response. (Committee Member) Awards, Prizes, & Fellowships George R. Brown Award for Superior Teaching, Rice University George R. Brown Prize for Excellence in Teaching, Rice University (2013) 2007 George R. Brown Award for Excellence in Teaching, Rice University (April 2007) George R. Brown Award for Superior Teaching, (2006) Outstanding Faculty Associate, Lovett College (2005) Ad hoc Reviewer, EMBO J., J. Biol. Chem., Am. J. Physiology, Genetics, Molecular & Cellular Biology, Yeast, Member, Genetics Society of America, Member, American Society for Cell Biology, Ad hoc Reviewer, National Science Foundation, Member, Genetics Society of America Member, American Society for Cell Biology Positions Held Faculty Fellow, Center for Teaching Excellence, Rice University. (2012 - 2015) Faculty Chair, CTE Fellows, Center for Teaching Excellence, Rice University. (2014 - 2015)