Dr. Mark Stayton

Department of Molecular Biology

University of Wyoming

Laramie, WY 82071

email: stayton@uwyo.edu

Statement of Research Interest

Molecular and Cellular Responses to Acute Myocardial Infarction

Cardiovascular disease is the single largest cause of death in westernized societies and the cost to treat acute myocardial infarction (AMI) in the United States alone is ~$5 billion per year.  For a given patient, predicting the risk of a future adverse cardiovascular event is difficult, despite family history and the use of clinical markers such as plasma lipid levels and protein markers of inflammation.  As a result, physicians and patients must make equivocal, and often expensive, therapeutic decisions based on incomplete information.  Furthermore, patients are frequently resistant to changing high-risk lifestyle habits, particularly when the danger seems remote or unspecified.

We are part of a multidisciplinary group* that is exploring molecular responses to AMI in a mouse surgical model.  We carry out open-heart surgery on mice and tie off the left anterior descending coronary artery thus inducing an acute myocardial infarction.  At intervals out to 48-h, we sacrifice the mice and measure 36,000 transcript concentrations in blood and three regions of the heart using Affymetrix mouse GeneChips.  As a control, we carry out a parallel time course analysis in mice which have undergone surgery, but without ligation of the coronary artery.  By comparing gene expression patterns between ischemic/infarcted mice and sham surgery controls at selected time points, we are developing models that classify LV myocardial gene expression patterns in response to ischemia and subsequent infarction.

Using the database as a starting point, we are addressing questions that include:  1) Do previously unrecognized genes play a role in the response of the left ventricle ( LV ) to infarction? 2) Can alterations in transcriptional processes be used to distinguish among signal transduction pathways that trigger the LV remodeling response? (3) Can the database be used to construct a comprehensive model for the matrix of reactions and their temporal expression that constitute the tissue response to infarction?  We are testing hypotheses derived from this expression database using the tools of biochemistry and cell biology and employing knock-out and transgenic mice.

*with the Department of Animal Science and the Department of Kinesiology and Health

Structure / Function Relationships In Heat-Stable Enzymes

It's now recognized that living organisms can be divided into three broad kingdoms: the eukaryotes, prokaryotes and the archaeans. The archaeans are microbes whose patterns of metabolism and gene structure / expression place them slightly closer to the eukaryotes than the prokaryotes. Archaeans have a predilection for extreme environments including high temperature niches such as deep-sea vents and terrestrial hot springs . At these temperatures, which often reach 100¡C, "normal" proteins denature and duplex DNA is melted. We have initiated studies of the heat-stable archaean enzyme, RadA. RadA is a homolog of the Rad51 (yeast) and RecA (E. coli ) proteins, which function, in homologous recombination by catalyzing strand exchange reactions.  My laboratory is over-produced these proteins in the mesophilic host, E. coli for studies of their structure and function. We are investigating the mechanisms that must operate within archaeans to control and catalyze recombination at temperatures above the melting point of duplex DNA.

Selected Publications

Hanekamp, T., D. Kobayashi, S. Hayes and M. M. Stayton (1997). “Avirulence gene D of Pseudomonas syringae pv. tomato may have undergone horizontal gene transfer.” FEBS Lett 415(1): 40-4.

Johnson, K. M., T. Hanekamp and M. M. Stayton (1997). “Methylene blue: An alternative, multi-purpose stain for detection, analysis and isolation of nucleic acids.” Biopolymers and Cell 13(3): 250-253.

Honzatko, R. B., M. M. Stayton and H. J. Fromm (1999). “Adenylosuccinate synthetase: recent developments.” Adv Enzymol Relat Areas Mol Biol 73: 57-102.

Farhatullah, K. M. Johnson, M. P. Brownson, M. M. Stayton and R. W. Groose (2003). “Soybean resistance to bacterial phytopathogens expressing avirulence gene D is mediated by a single gene (Rpg4) that is polymorphic throughout the germplasm.” Manuscript submitted.

Harpster, M., Amarendran, V., Gao, B., Gomelsky, M., McCormick, R. J., Stayton, M. M., and Thomas, D. P. Genome-wide transcription profiling post-MI. Physiologist, 45: 69, 2002.

Thomas, D. P., Bandyopadhyay, S., Stayton, M. M., Harpster, M., Amarendran, V., Pineguina, N., and McCormick, R. J. Earliest degradative and synthetic changes in mouse heart extracellular matrix post-myocardial infarction. In: Proceedings from the Scientific Conference on Molecular Mechanisms of Growth, Death and Regeneration in the Myocardium: Basic Biology and Insights into Ischemic Heart Disease and Heart Failure, Snowbird, UT, August 13-17, 2003 , pp. 44.

M Harpster; V Amarendran; S Bandyopadhyay ; R McCormick; D Thomas; M Stayton and M Gomelsky.  Expression of hypoxia-inducible genes in acute myocardial infarction in mice Symposium on Hypoxia. In:  Keystone Symposium "Biology of hypoxia: The role of oxygen sensing in development, normal function and disease"  2003.