David L. DeWitt

University Administrator Responsibilities

Associate Dean for Research and Budgets - College of Natural Science; Director, Research Technologies Support Facility - Office of the Vice President for Research and Graduate Studies

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

Mulabagal V, Subbaraju GV, Rao CV, Sivaramakrishna C, Dewitt DL, Holmes D, Sung B, Aggarwal BB, Tsay HS, Nair MG. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. 2009 Jul;23(7):987-92.

Mulabagal V, Lang GA, DeWitt DL, Dalavoy SS, Nair MG. Anthocyanin content, lipid peroxidation and cyclooxygenase enzyme inhibitory activities of sweet and sour cherries. J Agric Food Chem. 2009 Feb 25;57(4):1239-46.

Mulabagal V, Alexander-Lindo RL, Dewitt DL, Nair MG. Health-Beneficial Phenolic Aldehyde in Antigonon leptopus Tea. Evid Based Complement Alternat Med. 2009 May 19.

V Mulabagal, GA Lang, DL DeWitt, SS Dalavoy, MG Nair. Anthocyanin content, lipid peroxidation and cyclooxygenase enzyme inhibitory activities of sweet and sour cherries. J. Agric. Food Chem. ( Feb 25 2009) 57 1239-1246.

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.

MORE