Penn State University's Department of Veterinary Science: Grad Personnel

Jack P. Vanden Heuvel Professor of Molecular Toxicology
325 Life Sciences Building 814-863-8532 jpv2@psu.edu Web site: http://moltox.cas.psu.edu/research.html
Education: Postdoctoral training in molecular toxicology, National Institute of Environmental Health Sciences Ph.D., Environmental Toxicology, University of Wisconsin B.S., Pharmacology and Toxicology, University of Wisconsin
Teaching Interests Biochemical and molecular toxicology, pharmacology, carcinogenesis
Research: Mechanisms of action of hypolipidemic drugs and peroxisome proliferators, steroid hormone receptor-mediated signal transduction, signal transduction by lipids and fatty acids, receptor-mediated carcinogenesis Research in my laboratory focuses on how certain chemicals regulate gene expression, a very common theme in the biological discipline of molecular toxicology. We are examining a group of manmade chemicals called peroxisome proliferators. These chemicals are used as plasticizers and herbicides and also include clinically relevant drugs such as hypolipidemic and antidiabetic agents. In addition, recent evidence has shown that peroxisome proliferators are mimicking endogenous fatty acids, in that they regulate gene expression through the same mechanism as certain fatty acids. Because of the high likelihood of human and animal exposure, we are interested in how these chemicals result in disease in sensitive species so that we may assess possible health risks in other species. Also, by understanding the mechanism of action of peroxisome proliferators, we can better understand the biological role fatty acids play in differentia-tion and gene expression. Peroxisome proliferators cause their effects through activation of a steroid hormone receptor called peroxisome proliferator-activated receptor (PPAR). The basic mechanism of action of PPAR is similar to that of the estrogen and thyroid receptors, and several ongoing studies in my labora-tory dissect this pathway. The main issues of concern are how PPAR activity is being regulated and which genes are targets for this receptor that result in altered cellular function. PPAR has been implicated in many health conditions, including cancer, diabetes, and inflammation. Current research projects “Peroxisome proliferator-dependent gene regulation.” Funded by National Institutes of Health. “Biochemical characterization of PPAR.” Funded by National Institutes of Health. “Altered gene expression as a biological marker of exposure and responsiveness to classes of xenobiotics present in Pennsylvania’s environment.” Funded by Pennsylvania Department of Natural Resources. “Effects of conjugated linoleic acid on immune cells.” Funded by Pennsylvania Department of Agriculture.

Publications: Vanden Heuvel, J.P. (2000) Nuclear receptor: Peroxisome proliferator-activated receptors. In 2001 Yearbook of Science and Technology. Mark Licker, Publisher. The McGraw-Hill Companies. New York, NY. Pp 286-289. Kehrer J.P., Biswal S.S., La E., Thuillier P, Datta K., Fischer S.M., Vanden Heuvel J.P. (2001) Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J. 356, 899-906. Kumar, M.B., Ramadoss, P., Reen, R.K., Vanden Heuvel, J.P. and Perdew, G.H. (2001).The Q-rich sub-domain of the human Ah receptor transactivation domain is required for dioxin-mediated transcriptional activity. J. Biol. Chem. Nov 9;276(45):42302-10. Vanden Heuvel, J.P. and Peters, J.M. (2001). Biology of the PPAR family of receptors. Comments Toxicol. 7, 233-257. Yu, Y., Correll, P., and Vanden Heuvel, J.P. (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: Evidence for a PPARg-dependent mechanism. Biochim. Biophys. Acta. In Press Vanden Heuvel, J.P. (2002) Introduction to Molecular Toxicology, In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press Vanden Heuvel, J.P. (2002) Receptor Theory and the Ligand-Macromolecule Complex, In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press Vanden Heuvel, J.P. (2002) Control of Gene Expression, In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press Vanden Heuvel, J.P. (2002) Xenobiotic Receptor Systems: Introduction and Overview, In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press Peters, J.M. and Vanden Heuvel, J.P. (2002) Peroxisomes, peroxisome proliferators, and peroxisome proliferator-activated receptors (PPARs), In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press Vanden Heuvel, J.P. (2002) Alteration in Cell Signaling by Xenobiotics: Introduction and Overview, In: Cellular and Molecular Toxicology (Vanden Heuvel et al., eds.). Elsevier Science, Amsterdam, The Netherlands. In press