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Faculty

Jeff Peters

Associate Professor of Environmental Toxicology
312 Life Sciences Building
Telephone: 814-863-1387
FAX: 814-863-1696
Email: jmp21@psu.edu

Research Focus

Our laboratory studies the role of the peroxisome proliferator-activated receptors (PPARs) in the regulation of homeostasis, toxicology and carcinogenesis with extensive application of null mouse models. PPARs are members of the nuclear receptor superfamily and are critical modulators of environmental and dietary stimulii. Acting as regulatory transcription factors,  the PPARs modulate gene expression of target genes containing peroxisome proliferator responsive elements in response to ligand activation. Numerous genes that modulate lipid metabolism are regulated by PPAR and PPAR ligands/activators, and are clinically relevant for a number of diseases including diabetes, obesity, atherosclerosis and cancer. Our laboratory uses “knockout” and transgenic
mouse models to delineate the roles of PPARs, with a particular emphasis on epithelial cancers. Our goal is to identify new molecules/proteins that can be targeted with existing approaches to improve the efficacy of chemoprevention and chemotherapy.

PUBLICATIONS (selected from a total of 109)

• Burdick, A. D., Bility, M.T., Girroir, E. E., Billin, A.N., Willson, T.M., Gonzalez, F.J. and Peters, J.M. Ligand activation of peroxisome proliferator-activated receptor-/ (PPAR/) inhibits cell growth of human N/TERT-1 keratinocytes. Cellular Signaling (2007) 19: 1163-1171.
• Hollingshead, H.E., Girroir, E.E., Killins, R.L., Billin, A.N., Willson, T.M., Sharma, A., Amin, S., Gonzalez, F.J. and Peters, J.M.. Peroxisome proliferator-activated receptor-/ (PPAR/) ligands do not potentiate growth of human cancer cell lines. Carcinogenesis (2007) In Press.
• Hollingshead, H.E., Morimura, K., Adachi, M., Kennett, M.J., Billin, A.N., Willson, T.M., Gonzalez, F.J. and Peters, J.M.. PPAR/ protects against experimental colitis through a ligand-independent mechanism. Digestive Diseases and Sciences (2007) In Press.
• Shan, W., Nicol, C.J., Bility, M.T., Kennett, M.J., Ward, J.M., Gonzalez, F.J. and Peters, J.M.. Peroxisome proliferator-activated receptor  (PPAR) protects against chemically-induced liver toxicity. Hepatology (2007) In Press.
• Muller-Brusselbach, S., Komhoff, M., Burdick, A.D., Keil, B., Klose, K.J., Moll, R., Peters, J.M. and Muller, R.. Suppression of tumor angiogenesis and blockade of tumor growth in PPAR-deficient mice. EMBO Journal (2007) In Press.
• Ghosh, M., Wang, H., Ai, Y., Romeo, E., Luyendyk, J.P., Peters, J.M., Mackman, N., Dey, S.K. and Hla, T.. COX-2 suppresses tissue factor expression via endocannabinoid-directed PPAR activation. The Journal of Experimental Medicine (2007) In Press.
• Abdollahi, A., Schwanger, C., Kleef, J., Esposito, I., Domhan, S., Peschke, J., Hauser, K., Hahnfeldt, P., Hlatky, L., Debus, J., Peters, J.M., Freiss, H., Folkman, J. and Huber, P.E.. A transcriptional network governing the angiogenic switch: Evidence in human pancreatic carcinoma. Proceedings of the National Academy of Sciences (2007) In Press.
• Muller-Brusselbach, S., Ebrahimsade, S., Jakel, J., Eckhardt, J., Rapp, U.R., Peters, J.M., Moll, R. and Muller, R.. Growth of transgenic raf-induced lung adenomas is increased in mice with disrupted PPAR gene. International Journal of Oncology (2007) In Press.
• Coleman, J.D., Prabhu, K.S., Thompson, J.T., Reddy, S.P., Peters, J.M., Peterson, B.R., Reddy, C.C. and Vanden Heuvel, J.P.. The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the peroxisome proliferator-activated receptor-/ by. Free Radical Biology and Research  (2007) 42: 1155-1164.
• Woods, C.G., Burns, A.M., Maki, A., Bradford, B.U., Cunningham, M.L., Connor. H.D., Kadiiska, M.B., Mason, R.P., Peters, J.M. and Rusyn, I.. Sustained formation of -(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferators-activated receptor-, but not NADPH oxidase. Free Radical Biology and Medicine (2007) 42: 335-342.
• Klaunig, J.E., Babich, M.A., Cook, J.C., David, R.M., DeLuca, J.G., McKee, R.H., Peters, J.M., Roberts, R.A. and Fenner-Crisp, P.A.. PPAR and effects of TCE. Environmental Health Perspectives (2007) 115: A2-A3.
• Kim, D.J., Bility, M.T., Billin, A.N., Willson, T.M., Gonzalez, F.J. and Peters, J.M.. Peroxisome proliferator-activated receptor- selectively induces differentiation and inhibits cell proliferation. Cell Death and Differentiation  (2006) 13: 53-60.
• Burdick, A.D., Kim, D.J., Peraza, M.A., Gonzalez, F.J. and Peters, J.M.. The role of peroxisome proliferator-activated receptor- in epithelial cell growth and differentiation. Cellular Signaling (2006) 18: 9-22.
• Kim, D.J., Prabhu, K.S., Gonzalez, F.J. and Peters, J.M.. Inhibition of chemically-induced skin carcinogenicity by sulindac is independent of peroxisome proliferator-activated receptor  (PPAR). Carcinogenesis (2006) 27: 1105-1112.
• Marin, H.E., Peraza, M.A., Billin, A.N., Willson, T.M., Ward, J.M., Kennett, M.J., Gonzalez, F.J. and Peters, J.M.. Ligand activation of peroxisome proliferator-activated receptor  (PPAR) inhibits colon carcinogenesis. Cancer Research (2006) 66: 4394-4401.
• Peraza, M.A., Burdick, A.D., Marin, H.E., Gonzalez, F.J. and Peters, J.M.. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicological Sciences (2006) 90: 269-295.
• Lee, C.H., Olson, P., Hevener, A., Mehl, I., Chong, L.W., Olefsky, J.M., Gonzalez, F.J., Ham, H., Kang, H., Peters, J.M. and Evans, R.M. PPAR regulates glucose metabolism and insulin sensitivity. Proceedings of the National Academy of Sciences (2006) 103: 3444-3449.
• Rusyn, I., Peters, J.M. and Cunningham, M.L.. Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Critical Reviews in Toxicology (2006) 36: 459-479.
• Wang, Y., Botolin, D., Xu, J., Christian, B., Jayaprakasam, B., Nair, M., Peters, J.M., Busik, J., Olson, L.K. and Jump, D.B.. Regulation of hepatic elongase and desaturase expression in diabetes and obesity. Journal of Lipid Research (2006) 47: 2028-2041.
• Yang, Q., Yamada, A., Kimura, S., Peters, J.M. and Gonzalez, F.J.. Alterations in skin and stratified epithelia by constitutively activated PPAR. Journal of Investigative Dermatology (2006) 126: 374-385.
• Patel, R.D., Kim, D.J., Peters, J.M. and Perdew, G.H.. The Aryl hydrocarbon receptor directly regulates expression of the potent mitogen epiregulin. Toxicological Sciences (2006) 89: 75-82.
• Adachi, M., Kurotani, R., Morimura, K., Shah, Y., Sanford, M., Madison, B.B., Gumucio, D.L., Marin, H.E., Peters, J.M., Young, H.A. and Gonzalez, F.J.. PPAR in colonic epithelial cells protects against experimental inflammatory bowel disease. Gut (2006) 55: 1104-1113.
• Reed, K.R., Sansom, O.J., Hayes, A.J., Gescher, A.J., Peters, J.M. and Clarke, A.R.. PPAR status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer (2006) 6: 113.
• Peters, J.M., Cheung, C. and Gonzalez, F.J.. Peroxisome proliferator-activated receptor- (PPAR) and liver cancer: Where do we stand? Journal of Molecular Medicine  (2005) 83: 774-785.
• Kim, D.J., Murray, I., Burns, A.M., Gonzalez, F.J., Perdew, G.H. and Peters, J.M. Peroxisome proliferator-activated receptor- (PPAR) attenuates epidermal cell proliferation via ubiquitin-dependent down-regulation of kinase activity. The Journal of Biological Chemistry  (2005) 280:9519-9527.
• Hays, T., Rusyn, I., Burns, A.M., Gonzalez, F.J., Kennett, M.J., Ward, J.M. and Peters, J.M.. Role of the peroxisome proliferator-activated receptor  (PPAR) in bezafibrate-induced hepatocarcinogenesis. Carcinogenesis (2005) 26:219-227.
• Murray, I.A., Reen R.K., Leathery, N., Ramadoss, P., Bonati, L., Gonzalez, F.J., Peters, J.M., and Perdew G.H. Evidence that ligand binding is a key determinant of Ah receptor-mediated transcriptional activity. Archives of Biochemistry and Biophysics  (2005) 442: 59-71.
• Clemencet, M.C., Muzio, G., Trombetta, A., Peters, J.M., Gonzalez, F.J., Canuto, R.A. and Latruffe, N.. Differences in cell proliferation in rodent and human hepatic derived cell lines exposed to ciprofibrate. Cancer Letters (2005) 222: 217-226.
• Duez, H., Lefebvre, B., Poulain, P., Torra, I. P., Percevault, F., Luc, G., Peters, J.M., Gonzalez, F.J., Gineste, R., Helleboid, S, Fruchart, J.C., Fievet, C., Lefebvre, B. and Staels, B.. Regulation of human apo A-I by gemfibrizil and fenofibrate via selective peroxisome proliferator-activated receptor modulation. Arteriosclerosis, Thrombosis, and Vascular Biology  (2005) 25: 585-591.
• Polak, P., Kalinin, S., Russo, C.D., Gavrilyuk, V., Sharp, A., Peters, J.M., Richardson, J., Willson, T.M., Weinberg, G. and Feinstein, D.L.. Protective effects of a peroxisome proliferators-activated receptor-/ agonist in experimental autoimmune encephalomyelitis. Journal of Neuroimmunology (2005) 168: 65-75.
• Peters, J.M., Kato, S. and Gonzalez, F.J.. The United States-Japan workshop on: The role of nuclear receptors in carcinogenesis. Molecular Carcinogenesis (2004) 41:77-84.
• Harman, F., Nicol, C.J., Marin, H.E., Ward, J.M., Gonzalez, F.J. and Peters. J.M. Peroxisome proliferator-activated receptor- (PPAR) attenuates colon carcinogenesis. Nature Medicine  (2004) 10:481-483.
• Matsusue, K., Peters, J.M.* and Gonzalez, F.J.. Peroxisome proliferator-activated receptor  (PPAR) potentiates PPAR-stimulated adipogenesis.  The FASEB Journal (2004) 18:1477-1479. *Equally contributing first author.
• Kim, D.J., Akiyama, T. E., Harman, F., Burns, A.M., Shan, W., Ward, J.M., Kennett, M.J., Gonzalez, F.J. and Peters, J.M. PPAR)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis.  The Journal of Biological Chemistry  (2004) 279:23719-23727.
• Bility, M.T., Thompson, J., McKee, R.H., David, R.M., Butala, J.H., Vanden Heuvel, J.V. and Peters, J.M.. Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters. Toxicological Sciences (2004) 82:170-182.
• Rusyn, I., Asakura, S., Pachkowski, B., Bradford, B.U., Denissenko, M.F., Peters, J.M., Holland, S.M., Reddy, J.K., Cunningham, M.L. and Swenberg, J.A. Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: Identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators. Cancer Research  (2004) 64:1050-1057.
• Reed, K.R., Sansom, O.J., Hayes, A.J., Gescher, A.J., Winton, D.J., Peters, J.M. and Clarke, A.R.. PPAR status and APC-mediated tumourigenesis in the mouse intestine. Oncogene (2004) 23:8992-8996.
• Miyazaki, M., Dobrzyn, A., Sampath, H., Lee, S.-H., Man, W.C., Chu, K., Peters, J.M., Gonzalez, F.J. and Ntambi, J.M.. Reduced adiposity and liver steatosis by stearoyl-CoA desaturase deficiency are independent of peroxisome proliferator-activated receptor-. The Journal of Biological Chemistry (2004) 279:35017-35024.
• Akiyama, T.E., Lambert, G., Nicol, C.J., Matsusue, K., Peters, J.M., Brewer Jr., H.B. and Gonzalez, F.J.. Peroxisome proliferator-activated receptor  regulates very low density lipoprotein production and catabolism in mice on a western diet. The Journal of Biological Chemistry (2004) 279:20874-20881.
• Nicol, C.J., Yoon, M., Ward, J.M., Yamashida, M., Fukamachi, K., Peters, J.M. and Gonzalez, F.J.. PPAR deficiency increases susceptibility to DMBA-induced mammary and skin carcinogenesis. Carcinogenesis (2004) 25:1747-1755.
• Nakajima, T., Kamijo, Y., Tanaka, N., Fukushima, Y., Tanaka, E., Kiyosawa, K., Peters, J.M., Gonzalez, F.J. and Aoyama, T. Peroxisome proliferator-activated receptor  (PPAR) protects against alcohol-induced liver damage. Hepatology  (2004) 40:972-980.
• Peters, J.M., Aoyama, T., Burns, A.M. and Gonzalez, F.J.. Bezafibrate is a dual ligand for PPAR and PPAR: Studies using null mice. Biochimica Biophysica Acta-Molecular and Cell Biology of Lipids (2003) 1632:80-89.
• Tien, E.S., Gray, J.P., Peters, J.M. and Vanden Heuvel, J.P.. Comprehensive gene expression analysis of peroxisome proliferator-treated immortalized hepatocytes from the PPAR-null mouse. Cancer Research  (2003) 63:5767-5780.
• Klaunig, J.E., Babich, M.A., Baetcke, K.P., Cook, J.C., Corton, J.C., David, R.M., DeLuca, J.G., Lai, D.Y., McKee, R.H., Peters, J.M., Roberts, R.A. and Fenner-Crisp, P.A.. PPAR agonist-induced rodent tumors: Mode(s) of action and human relevance. Critical Reviews in Toxicology (2003) 33:655-780.
• Rosenberger, T.A., Hovda, J.T. and Peters, J.M.. Targeted disruption of peroxisomal proliferator-activated receptor ) results in distinct gender differences in mouse brain phospholipid and esterified FA levels. Lipids (2002) 37:495-500.
• Rao, M.S., Peters, J.M., Gonzalez, F.J. and Reddy, J.K.. Hepatic regeneration in peroxisome proliferator-activated receptor -null mice after partial hepatectomy. Hepatology Research  (2002) 22:52-57.
• Ripp, S.L., Fitzpatrick, J.L., Peters, J.M. and Prough, R.A.. Induction of CYP3A Expression by DHEA: Involvement of the Pregnane X Receptor. Drug Metabolism and Disposition (2002) 30:570-575.
• Ntambi, J.M., Choi, Y., Park, Y., Peters, J.M. and Pariza, M.W.. Effects of conjugated linoleic acid (CLA) on immune responses, body composition and stearoyl-CoA desaturase. Canadian Journal of Applied Physiology (2002) 27:617-627.
• Reynolds, K., Novosad. B., Hoffhines, A., Gipson, J., Johnson, J., Peters, J., Gonzalez, F., Gimble, J. and Hill, M.. Pretreatment with troglitazone decreases lethality during endotoxemia in mice. Journal of Endotoxin Research (2002) 8:307-314.