John P. Vanden Heuvel
Assistant Professor of Molecular Toxicology
Appointed to the Department of Veterinary Science: 1997
Please see "Jack's
Research Interest and Links Page"
Education:
- Post-doc. Molecular Toxicology, National Institute of Environmental
Health Sciences, 1993
- Ph.D. Environmental Toxicology, University of Wisconsin, 1991
- B.S. Pharmacology and Toxicology, University of Wisconsin, 1986
Teaching Areas:
- Biochemical and molecular toxicology
- Pharmacology
- Carcinogenesis
Research and Scholarship Areas:
- 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
The primary goal of my research is to examine the effects of certain exogenous chemicals ("xenobiotics") on the regulation of gene expression in mammalian cells and understand how these effects may result in toxicity, including cancer. The compounds being studied in our laboratory are the receptor-mediated tumor promoters, which include a group of hypolipidemic drugs, lipids and pollutants known as peroxisome proliferators. The effect of peroxisome proliferators on gene regulation is largely attributed to activation of a novel member of the steroid hormone receptor superfamily called peroxisome proliferator-activated receptor (PPAR). In addition to being affected by peroxisome proliferators, PPAR is the intracellular receptor involved in many of the biological effects of fatty acids. Three critical questions are being asked in our current research efforts: 1). What genes are being regulated by PPAR and of these, which are causally related to tumor promotion? To answer this question we use a variety of techniques including differential-display polymerase chain reaction. As the result of these studies, we have identified a novel transcription factor called rZFP-37 that may be a crucial link between PPAR and growth regulation; 2). How are ligand, protein-protein interactions, and phosphorylation regulating PPAR activity? Of particular interest are the interactions between PPAR and heat shock proteins as well as the convergence of growth factor and PPAR signal transduction pathways; and, 3). Does the dietary fatty acid conjugated linoleic acid (CLA) result in its effects via a PPAR-dependent manner? CLA is particularly interesting since it has been reported to have anti-cancer and anti-atherosclerotic activity and our lab has demonstrated that it has beneficial effects in the treatment of diabetes. The result of studies in all three areas has helped us to appreciate how peroxisome proliferators affect gene expression. In addition, since peroxisome proliferators mimic natural fatty acids, this research has answered some fundamental biological questions about PPAR's role in lipid homeostasis.
Current Research Projects:
- "Peroxisome proliferator-dependent gene regulation". Funded
by NIEHS (R29 FIRST Award) until 2001
- "Biochemical Characterization of PPAR". Funded by NIEHS (R01,
co-Principal Investigator) until 2000
- "Modulation of peroxisome proliferation and hepatocarcinogenesis
by dietary conjugated linoleate." Funded by American Institute for
Cancer Research, (Co-principal investigator) until 1999
- "Modulation of diabetes by conjugated linoleic acid".
Funded by National Cattlemen's Beef Association
Selected Publications since 1997:
1. Perdew, G. H., Weigand, H., Vanden Heuvel, J. P., Mitchell, C. and Singh, S. S. (1997) A 50 kDa protein associated with Raf and pp60v-src protein kinases is a mammalian homolog of the cell cycle control protein cdc37. Biochemistry 36, 3600-3607.
2. Belury, M.A. and Vanden Heuvel, J.P. (1997). Protection against cancer and heart disease by the dietary fatty acid, conjugated linoleic acid: Potential mechanisms of action. Nutr. Disease Update 1, 58-63
3. Belury, M.A., Moya-Camarena, S.Y, Liu, L.-Li, and Vanden Heuvel, J.P. (1997). Dietary conjugated linoleic acid induces peroxisome-specific enzyme accumulation and ornithine decarboxylase activity in mouse liver. J. Nutr. Biochem. 8, 579-584.
4. Martinez, E., Moore, D.D., Keller, E., Pearce, D., Vanden Heuvel, J.P., Robinson, V., Gottlieb, B., MacDonald, P., Simons Jr, S., Sanchez, E., Danielsen, M. (1998) The Nuclear Receptor Resource: a growing family. Nucleic Acids Res. 26: 241-243
5. Meyer, B.K., Pray-Grant, M.G., Vanden Heuvel, J.P., and Perdew, G.H. (1998). Hepatitis B Virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Molec. Cell. Biol. 18: 978-988
6. Houseknecht, K.L., Vanden Heuvel, J.P., Portocarrero, C.P., Peck, L.W., Nickel, K.P., Belury, M.A. (1998). Dietary Conjugated Linoleic Acid Normalizes Impaired Glucose Tolerance in the Zucker Diabetic Fatty fa/fa Rat. Biochem. Biophys. Res. Commun.. 244: 678-682.
7. Belury, M.A., Moya-Camarena, S.Y. , Sun, H., Snyder, E., Davis II, J.W., Cunningham, M.L., and Vanden Heuvel, J.P. (1998). Comparison of dose-response relationships for induction of lipid metabolizing and growth regulatory genes by peroxisome proliferators in rat liver. Toxicol. Appl. Pharmacol. 151, 254-261.
8. Vanden Heuvel, J.P. Holden, P., Tugwood, J., Ingle, C., Yen, W.Y., Snyder, E., Galjart, N., Greenlee, W.F. (1998). Identification of a novel peroxisome proliferator responsive cDNA isolated from rat hepatocytes as the zinc-finger protein ZFP-37. Toxicol. Appl. Pharmacol. In press.
9. Kane, M.D., Vanden Heuvel, J.P., Isom, G.E., and Schwarz, R.D. (1998) Differential expression of group I metabotropic glutamate receptors (mGluRs) in PC12 cells: Role of nerve growth factor and ras. Neurosci. Lett. 252, 1-4.
10. Vanden Heuvel, J.P. and Davis II, J.W. (1998) Molecular approaches to identify exposure and risk to specific environmental pollutants. Biomarkers, In Press
11. Vanden Heuvel, J.P. (1998) Peroxisome Proliferator-Activated Receptors (PPARs) and carcinogenesis. Toxicol. Sci., In Press
12. Vanden Heuvel, J.P. (1998) Peroxisome Proliferator Activated Receptors: A Critical Link between Fatty Acids, Gene Expression and Carcinogenesis. J. Nutr., In Press
13. Belury, M.A. Houseknecht, K.L., and Vanden Heuvel, J.P. Conjugated Linoleic Acid Modulates Adipose Lipid Composition, Plasma Triglyceride and Leptin Levels in the Zucker Fatty fa/fa Rat. J. Nutr., Submitted
14. Moya-Camarena, S.Y., Vanden Heuvel, J.P. and Belury, M.A. Conjugated linoleic acid activates peroxisome proliferator-activated receptor a and b subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats. Biochim. Biophys. Acta In Press
Books Edited and Chapters Authored:
Vanden Heuvel, J.P., Bell, D.A., Corton, C. and Mattes, W. PCR Applications in Molecular Toxicology (Vanden Heuvel, J.P. ed). CRC Press, Boca Raton FL. 1997. 237 pages
J.P. Vanden Heuvel (1997). Analysis of gene expression. In: PCR Applications in Molecular Toxicology (Vanden Heuvel, J.P. ed). CRC Press, Boca Raton FL, pp. 41-98
J.P. Vanden Heuvel (1997). Cloning by PCR. In: PCR Applications in Molecular Toxicology (Vanden Heuvel, J.P. ed). CRC Press, Boca Raton FL, pp. 121-162.
J.P. Vanden Heuvel (1997). General molecular biology techniques. In: PCR Applications in Molecular Toxicology (Vanden Heuvel, J.P. ed). CRC Press, Boca Raton FL, pp. 177-212.
Vanden Heuvel, J.P. (1998). Approaches for the identification of xenobiotic-inducible genes, In: Toxicant-receptor interactions. Modulation of signal transduction and gene expression (M.S. Denison and W.G. Helferich, eds.) Taylor and Francis, Philadelphia, PA., pp. 217-235.
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Dr. Vanden Heuvel