Michael Thompson

Instructor

Ph.D., University of Kentucky School of Medicine

Phone: 812-237-2403

Email: Michael.Thompson@indstate.edu

Office: Science Building 287F

Thompson Laboratory - Overview

A better understanding to the body’s natural responses to disease and infection is crucial to the development of novel drugs and therapeutic interventions. First and foremost among these responses is inflammation, a necessary local tissue response to damage, disease, or infection that activates both the innate and adaptive immune systems and initiates the tissue repair process. Therefore, my laboratory is focused on understanding the interactions between the various proteins and enzymes that are involved in the inflammatory response, how they are regulated, and how various infectious agents interact with these proteins.

Regulation of Leukotriene A₄ Hydrolase

Leukotriene A₄ hydrolase (LTA4H) is a dual-function zinc metallopeptidase and epoxide hydrolase that has been implicated in many inflammatory pathologies, and has thus become a popular drug target. LTA4H converts leukotriene A₄ into leukotriene B₄, which acts as a chemoattractant agent for neutrophils during the early stages of an inflammatory response. High levels of the enzyme contribute to the pathogenesis of numerous cancers and may also lead to plaque instability in atherosclerosis. Thus, a better understanding of the biochemical regulation of LTA4H and the identification of factors that interact with the enzyme will likely further elucidate its role in these processes and lead to more effective treatment options.

Interactions of Matrix Metalloproteinase-2 and Apolactoferrin

Matrix metalloproteinases have been implicated in the maladaptive changes that are caused by hypertension, atherosclerosis, and tumor development. In particular, matrix metalloproteinase-2 (MMP-2) has been linked to the progression of atherosclerosis and to the abnormal tissue repair processes following acute myocardial infarction, making it an attractive therapeutic target in these pathologies. My laboratory has previously discovered and characterized an interaction between MMP-2 and apolactoferrin (ApoLTF) that inhibits the enzyme’s activity at temperatures of 38°C and above; however, there is still much to learn about this interaction and its effects on overall extracellular matrix remodeling and various disease processes.

Commitment to Student Education and Research Experiences

With more than 25 years of research experience, I have involved numerous undergraduate and graduate students in my research. Many of these students have served as co-authors on publications from my laboratory, and have gone on to prestigious careers of their own in science, education, and medicine. If you are interested in research opportunities in my laboratory, please feel free to reach out to me by e-mail.

Selected Publications

1. Seipelt, RL, Bailey FC, Schaible A, and Thompson MW. (2010). Asn₃₆₂ is essential for zinc binding and catalysis in the peptidase reaction of Saccharomyces cerevisiae leukotriene A₄ hydrolase. Biochimica et Biophysica Acta Proteins and Proteomics 1804, 2070-2076.

2. Thompson MW, Beasley KA, Schmidt MD, and Seipelt RL. (2009). Arginyl aminopeptidase-like 1 (RNPEPL1) is an alternatively processed aminopeptidase with specificity for methionine, glutamine, and citrulline residues. Protein and Peptide Letters 16, 1256-1266.

3. Tharp AC, Laha M, Panizzi P, Thompson MW, Fuentes-Prior P, and Bock PE. (2009). Plasminogen substrate recognition by the streptokinase-plasminogen catalytic complex is facilitated by Arg253, Lys256, and Lys257 in the streptokinase -domain and kringle 5 of the substrate. Journal of Biological Chemistry 284, 19511-19521.

4. Newsome AL, Johnson JP, Seipelt RL, and Thompson MW. (2007). Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation.  Biochemistry and Cell Biology 85, 563-572.

5. Thompson MW, Archer ED, Romer CE, and Seipelt RL. (2006). A conserved tyrosine residue is essential for transition state stabilization in Saccharomyces cerevisiae leukotriene A₄ hydrolase.  Peptides 27, 1701-1709.

6. Thompson, MW, Govindaswami M, and Hersh LB. (2003). Mutation of active site residues of the puromycin-sensitive aminopeptidase: conversion of the enzyme into a catalytically inactive binding protein. Archives of Biochemistry and Biophysics 413, 236-242.

7. Thompson MW and Hersh LB. (2003). Analysis of conserved residues of the human puromycin-sensitive aminopeptidase. Peptides 24, 1359-1365.

8. Ma Z, Daquin A, Yao J, Rodgers D, Thompson MW, and Hersh LB. (2003). Proteolytic cleavage of the puromycin sensitive aminopeptidase generates a substrate binding domain. Archives of Biochemistry and Biophysics 415, 80-86.

9. Stoltze, L, Schirle M, Schwarz G, Schroter C, Thompson MW, Hersh LB, Kalbacher H, Stevanovic S, Rammensee HG, and Schild H.  (2000). Two new proteases in the MHC class I processing pathway. Nature Immunology 1, 413-418.

10. Thompson MW, Tobler AR, Fontana A, and Hersh LB. (1999). Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. Biochemical and Biophysical Research Communications 258, 234-240.

Selected National and International Presentations

1. Thompson MW. Ceruloplasmin binds and inhibits matrix metalloproteinase-2. American Society for Biochemistry and Molecular Biology 2012 Conference (ASBMB), San Diego, CA, April 2012.

2. Thompson MW, Schaible A, and Seipelt RL. Asn₃₆₂ contributes to zinc binding by leukotriene A4 hydrolase. American Society for Biochemistry and Molecular Biology 2010 Conference (ASBMB), Anaheim, CA, April 2010.

3. Thompson MW, Mohyuddin N, and Seipelt RL. Localization of proteolytic forms of MMP-2 in normal and autoimmune thyroid tissues. American Society for Cell Biology 2009 Conference (ASCB), San Diego, CA, December 2009.

4. Thompson MW, Beasley KA, Archer ED, and Seipelt RL. Asn₃₆₂ contributes to zinc binding by leukotriene A4 hydrolase. American Society for Cell Biology 2008 Conference (ASCB), San Francisco, CA, December 2008.

5. Newsome AL, Johnson JP, Seipelt RL, and Thompson MW. Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by a zinc chelation mechanism. American Society for Cell Biology 2007 Conference (ASCB), Washington, DC, December 2007.

6. Thompson MW and Seipelt RL. Arginyl aminopeptidase-like 1 (RNPEPL1) is a ubiquitously expressed, alternatively processed metallopeptidase with preference for neutral and aromatic amino acids. American Society for Cell Biology 2006 Conference (ASCB), San Diego, CA, December 2006.

7. Thompson MW, Archer ED, Terry AN, and Seipelt RL. Halide ions alter substrate specificity of Saccharomyces cerevisiae leukotriene A4 hydrolase but do not increase catalytic efficiency. Experimental Biology 2006 Conference (ASBMB), San Francisco, CA, April 2006.

8. Archer ED, Seipelt RL, and Thompson MW. A conserved tryptophan residue with an altered pKa is essential for the peptidase reaction of Saccharomyces cerevisiae leukotriene A₄ hydrolase. Experimental Biology 2006 Conference (ASBMB), San Francisco, CA, April 2006.

9. Thompson MW, Romer CE, and Seipelt RL. Two conserved tyrosine residues are essential for the peptidase activity of Saccharomyces cerevisiae leukotriene A₄ hydrolase. Experimental Biology 2005 Conference (ASBMB), San Diego, CA, April 2005.

10. Thompson, MW, Tobler, A, Fontana, A, and Hersh, LB. Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. International Neuropeptide Society 2000 Summer Neuropeptide Conference, Sainte-Adele, Quebec, Canada, July 2000.