---

Education:

• B.S. 1967 University of Wisconsin-Madison
• Ph.D. 1972 Pharmacology Marquette University School of Medicine

Overview

Richard received his B.S. degree (1967) from the University of Wisconsin-Madison and his Ph.D. degree in pharmacology (1972) from the Marquette University School of Medicine (now the Medical College of Wisconsin). He joined the faculties of the School of Pharmacy and the Environmental Toxicology Center at the University of Wisconsin-Madison in 1975. He currently serves as Deputy Director of the NIEHS Center for Developmental and Molecular Toxicology. His research interests are in toxicology.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant which elicits a wide range of toxic responses. The developing male rat reproductive system is 100 times more sensitive to TCDD than is its adult counterpart. In utero and lactational exposure to a single low dose delays testis descent and preputial separation, decreases testis, epididymis, and accessory sex organ weights, and decreases daily sperm production, epididymal sperm reserves, and ejaculated sperm numbers throughout development. The mechanism underlying the spectrum of toxic responses elicited by TCDD is poorly understood. TCDD binds the aryl hydrocarbon receptor (AhR), which translocates to the nucleus and dimerizes with the AhR nuclear translocator (ARNT). This complex, a ligand-activated transcription factor, binds to enhancer elements (DREs) in the 5' regulatory region of genes and activates transcription. Although none of the TCDD-responsive genes identified to date have been directly linked to toxicity, it is thought that induction or repression of transcription of genes which have not yet been identified may play a key role in eliciting toxic responses. To better understand the mechanism by which TCDD selectively impairs the developing male reproductive system, we are characterizing the ontogeny and distribution of the AhR and ARNT within this organ system. In addition, we are working to identify genes that are transcriptionally modulated by in utero and lactational TCDD exposure in the prostate and epididymis, two organs which are particularly sensitive to this treatment. The identification of a TCDD-responsive gene(s) with known function may provide insight into the mechanism by which TCDD affects growth and/or function of the prostate, epididymis, and perhaps other organs as well. Novel genes will require characterization before mechanistic hypotheses can be formulated.

Work-Related Interests/Research:

Toxicology

Highlighted Publications:

• Powers, B.E., Lin, T.-M., Vanka, A., Peterson, R.E., Juraska, J.M., and Schantz, S.L.: Tetrachlorodibenzo-p-dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR+/- mice. Genes, Brain and Behavior 4: 51-59, 2005.
• Antkiewicz, D.S., Burns, G.C., Carney, S.A., Peterson, R.E., and Heideman, W.: Heart malformation is an early response to TCDD in embryonic zebrafish. Toxicol. Sci. 84: 1-10, 2005.
• Hill, A.J., Teraoka, H., Heideman, W. and ,Peterson, R.E.: Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol. Sci. 86: 6-19, 2005.
• Mukai, M., Dong, Q., Hardy, M.P., Kiyokawa, H., Peterson, R.E., and Cooke, P.S.: Altered prostatic epithelial proliferation, apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors. Biol. Repro. 73, 951-958, 2005.
• Heideman, W., Antkiewicz, D.S., Carney, S.A., and Peterson, R.E.: Zebrafish and cardiac toxicology. Cardiovasc. Toxicol. 5: 203-214, 2005.
• Lipinski, R.J., Cook, C.H., Barnett, D.H., Gipp, J.J., Peterson, R.E., and Bushman, W.: Sonic hedgehog signaling regulates the expression of Insulin-like growth factor binding protein-6 during fetal prostate development. Dev. Dyn. 233: 829-836, 2005.
• Fritz, W.A., Lin, T.-M., Moore, R.W., Cooke, P.S., and Peterson, R.E.: In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Effects on the prostate and its response to castration in senescent C57BL/6J mice. Toxicol. Sci. 86: 387-395, 2005.
• Doles, J.D., Vezina, C.M., Lipinski, R.J., Peterson, R.E., and Bushman, W.: Growth, morphogenesis, and differentiation during mouse prostate development in situ, in renal grafts, and in vitro. Prostate 65 (4): 390-399, 2005.
• Carney, S.A., Prasch, A.L., Heideman, W., and Peterson, R.E.: Understanding dioxin developmental toxicity using the zebrafish model. Birth Defects Research, Part A: Clinical and Molecular Teratology 76: 7 -18, 2006.
• Prasch, A.L., Tanguay, R.L., Mehta, V., Heideman, W., and Peterson, R.E.: Identification of zebrafish ARNT1 homologs: TCDD developmental toxicity in zebrafish requires ARNT1. Mol. Pharmacol. 69: 776-787, 2006.
• Ito, T., Nagai, H., Lin, T.-M., Peterson, R.E., Tohyama, C., Kobayashi, T., and Nohara, K.: Organic chemicals adsorbed onto diesel exhaust particles directly alter the differentiation of fetal thymocytes through aryl hydrocarbon receptor but not oxidative stress responses. J. Immunotoxicology 3: 21-30, 2006.
• Carney, S.A., Chen, J., Burns, C.G., Xiong, K.M., Peterson, R.E., and Heideman, W.: AHR activation produces heart-specific transcriptional and toxic responses in developing zebrafish. Molec. Pharmacol. 70: 1-13,2006.
• Jurgella, G.F., Marwah, A., Malison, J.A., Peterson, R.E., and Barry, T.P.: Effects of xenobiotics and steroids on estrogen metabolism in lake trout.Gen. Comp. Endocrinol. 148:273-281, 2006.
• van den Berg, M., Birnbaum, L., Denison, M., De Vito, M., Farland, W., Feeley, M., Fiedler, H., Hakansson, H., Hanberg, A., Haws, L., Rose, M., Safe, S., Schrenk, D., Tohyama, C., Tritscher, A., Tuomisto, J., Tysklind, M., Walker, N., and Peterson, R.E.: The 2005 World Health Organization re-evaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol. Sci. 93: 223-241, 2006.
• Antkiewicz, D.S., Peterson, R.E., Heideman, W.: Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Sci. 94: 175 -182, 2006.
• Fritz, W.A., Lin, T.-M., Cardiff, R.D. and Peterson, R.E.: The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. Carcinogenesis 28(2): 497-505, 2007.
• Cook, C., Vezina, C.M., Hicks, S.M., Shaw, A., Elkahwaji, J., Peterson, R.E., and Bushman, W.: Noggin is required for normal lobe patterning and ductal budding in the mouse prostate. Dev. Biol., 2007. (Submitted)
• Kim, K.H., Antkiewicz, D.S., Kim, T.G., Heideman, W., Peterson, R.E., and Lee, Y.: Lrrc10 is required for early heart development and function in zebrafish. Dev. Biol. , 2007. (Submitted)
• King Heiden, T.C., Dengler, E. Kao, W.J., Heideman, W. and Peterson, R.E.: Developmental toxicity of low generation dendrimers in zebrafish: Influence of RGD-conjugation. Toxicol. Appl. Pharmacol., 2007.
• Song, J., Clagett-Dame, M., Hahn, M.E., Peterson, R.E., and DeLuca, H.F.: The production and inactivation of an endogenous AhR ligand. Arch. Biochem. Biophys., 2007. (Submitted)
• Wu, Q., Suzuki, J.S., Zaha, H., Nohara, K., Lin, T.-M., Peterson, R.E., Takei, T., Tohyama, C., and Ohsako, S.: Differences in hepatic gene expression induced by TCDD among different mouse strains with identical AhR genotypes. Pharmacogenetic, 2007. (Submitted)
• Hill, A.J., King Heiden, T., Heideman, W., and Peterson, R.E.: Roles of ARNT2 in zebrafish embryonic development. Zebrafish, 2007. (Submitted)
• Mehta, V., Peterson, R.E., and Heideman, W.: AHR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin induces heart valve defects. Dev. Biol., 2007. (Submitted)
• Chen, J., Carney, S.A.,Peterson, R.E., and Heideman, W.: Retinoic acid induced cardiotoxicity in the zebrafish embryo: Microarray studies identify Nr2F5 as a critical target. Mol. Cell. Biol., 2007. (Submitted)