David L. DeWitt
Professor
Assoc Dean - CNS
Director - RTSF
  • B.S. 1976, University of California, Davis
  • Ph.D. 1982, Michigan State University
  • Postdoctoral Fellow, 1982-85, La Jolla Cancer Research Foundation

dewittd@msu.edu
519A Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-353-5284
Lab: 517-432-2141


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David L. DeWitt

Research Interests

Our research focuses on the study of the enzymes that produce prostaglandins. These enzymes, referred to as PGH synthases, are the site of action of non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen, and, thus, are important regulators of inflammation, and also mitogenesis. We are examining several aspects of these enzymes, including:

  • a) regulation of expression, including promoter analysis of transcriptional activation;
  • b) translational regulation — many of the inflammatory response genes are translationally regulated;
  • c) cellular biology of how these enzymes are coupled to specific phospholipases responsible for providing fatty acid substrate, and subsequent channeling of prostaglandin products to different intracellular and extracellular locations; and
  • d) regulation of expression of these enzymes by environmental toxicants —

we have recently found that TCDD is an inducer of PGH synthase in certain cell types and are examining how PGH synthase expression may be involved in the toxic response of this and other xenobiotics. Studies have shown that use of aspirin is related to a reduced incidence of colon cancer, and we are also beginning to examine the role of prostaglandin production in the development of colon cancer.

Recent Publications

Raman P, Dewitt DL, Nair MG. Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acidic aqueous extracts of some dietary supplements. Phytother Res. 2008 Feb;22(2):204-12.

Mulabagal V, Van Nocker S, Dewitt DL, Nair MG. Cultivars of apple fruits that are not marketed with potential for anthocyanin production. J Agric Food Chem. 2007 Oct 3;55(20):8165-9.

Cuendet M, Mesecar AD, DeWitt DL, Pezzuto JM. An ELISA method to measure inhibition of the COX enzymes. Nat Protoc. 2006;1(4):1915-21.

Mbonye UR, Wada M, Rieke CJ, et al. The 19-amino acid cassette of cyclooxygenase-2 mediates entry of the protein into the endoplasmic reticulum-associated degradation system Journal of Biological Chemistry 281 (47): 35770-35778 Nov 24 2006.

MirAfzali Z, Leipprandt JR, McCracken JL, et al. Topography of the prostaglandin endoperoxide H-2 synthase-2 in membranes Journal of Biological Chemistry 281 (38): 28354-28364 Sep 22 2006.

Adhikari DP, Schutzki RE, DeWitt DL, et al. Effects of Amelanchier fruit isolates on cyclooxygenase enzymes and lipid peroxidation Food Chemistry 97 (1): 56-64 Jul 2006.

Jankun J, Aleem AM, Malgorzewicz S, et al. Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells Molecular Cancer Thearpeutics 5 (5): 1371-1382 May 2006.

MirAfzali Z, Leipprandt JR, McCracken JL, DeWitt DL. Fast, efficient reconstitution of the cyclooxygenases into proteoliposomes. Arch Biochem Biophys. 2005 Nov 15;443(1-2):60-5. Epub 2005 Sep 15.

Zhang Y, Dewitt DL, Murugesan S, Nair MG. Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds. Life Sci. 2005 Nov 4;77(25):3222-30. Epub 2005 Jun 23.

Garavito RM, Malkowski MG, DeWitt DL. The structures of prostaglandin endoperoxide H synthases-1 and -2. Prostaglandins Other Lipid Media. 69:129-152 (2002)

Proshlyakov, D.A., Pressler, M.A., DeMaso, C., Leykam, J.F., Dewitt, D.L. and Babcock, G.T. The missing link in cytochrome oxidase: Y244 is redox-active in O2 activation and reduction. Science, 290:1588-1591 (2000).

Smith, T., Leipprandt, J., and D. L. DeWitt. Purification and Characterization of the Human Recombinant Histidine-Tagged Prostaglandin Endoperoxide H Synthases -1 and -2. Arch. Biochem. 375 :195-200 (2000). MORE