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Christopher A. Bradfield, Ph.D.

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C. Bradfield photo Professor of Oncology

B.Sc., 1982, Environmental Toxicology, University of California at Davis
Ph.D., 1986, Toxicology/Nutrition, University of California at Berkeley
Postdoctoral research: McArdle Laboratory, University of Wisconsin-Madison

Office: 213A McArdle Laboratory
Telephone: Office - (608) 262-2024; Lab (608) 262-1209
Email: bradfield@oncology.wisc.edu

Lab Home Page

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Research Interests: Molecular biology of the PAS family of proteins

Research Description: Our laboratory is interested in a family of transcriptional regulators known as PAS proteins. Members of this emerging family of proteins control a number of processes, including xenobiotic metabolism (Ah-receptor and Arnt), circadian rhythms (Per), angiogenesis (HIF1a and Arnt), and neurogenesis (Sim). The model system that is currently emphasized is the signal transduction pathway mediated by Ah-receptor/Arnt heterodimeric complex. These helix-loop-helix-PAS proteins regulate the induction of a number of xenobiotic metabolizing enzymes that occur in response to exposure to a variety of polycyclic aromatic environmental pollutants. In addition, the Ah-receptor mediates a second battery of genes responsible for a number of "toxic effects" of dioxins, such as epithelial hyperplasia, immunosuppression, teratogenesis, and tumor promotion.

To understand these proteins and their signal transduction pathways, we are focusing on the characterization of the Ah-receptor/Arnt pathway in genetically manipulable organisms such as mice and yeast. We use yeast genetics as a method to identify genes that are required for signaling. In addition, the yeast system is proving valuable in modifier screens to identify novel components of the dioxin signaling pathway. Experiments in the murine system help us to understand the physiological function of these proteins, as well as to identify new members of the PAS family. Current areas of interest include the use of gene-targeting to generate informative bHLH-PAS loci and the use of more classical transgenic approaches to construct murine models that will help us characterize the mechanisms that underlie the toxicological and developmental effects of halogenated aromatics like dioxin.

Selected recent publications

Kennedy, G. D., Nukaya, M., Moran, S. M., Glover, E., Weinberg, S., Balbo, S., Hecht, S. S., Pitot, H. C., Drinkwater, N. R., and Bradfield, C. A.  Liver Tumor Promotion by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin is Dependent on the Aryl Hydrocarbon Receptor and TNF/IL-1 Receptors.  Toxicol. Sci., in press, 2014 [Epub ahead of print Apr 9 2014].

Sievers, C. K., Shanle, E. K., Bradfield, C. A., and Xu, W.  Differential Action of Monohydroxylated Polycyclic Aromatic Hydrocarbons with Estrogen Receptors a and β.  Toxicol. Sci., 132(2): 359-367, 2013.

Lee, J. S., Cella, M., McDonald, K. G., Garlanda, C., Kennedy, G. D., Nukaya, M., Mantovani, A., Kopan, R., Bradfield, C. A., Newberry, R. D., and Colonna, M.  AHR Drives the Development of Gut ILC22 Cells and Postnatal Lymphoid Tissues via Pathways Dependent On and Independent of Notch.  Nat. Immunol., 13:  144-151, 2012.

Mezrich, J. D., Nguyen, L. P., Kennedy, G., Nukaya, M., Fechner, J. H., Zhang, X., Xing, Y., and Bradfield, C. A.  SU5416, a VEGF Receptor Inhibitor and Ligand of the AHR, Represents a New Alternative for Immunomodulation.  PLoS One, 7(9):e44547, 2012.

Paschos, G. K., Ibrahim, S., Song, W.-L., Kunieda, T., Grant, G., Reyes, T. M., Bradfield, C. A., Vaughan, C. H., Eiden, M., Masoodi, M., Griffin, J. L., Wang, F., Lawson, J. A., and FitzGerald, G. A.  Obesity in Mice with Adipocyte-specific Deletion of Clock Component Arntl.  Nat. Med., 18: 1768-1777, 2012.

Pauly, S. K., Fechner, J. H., Zhang, X., Torrealba, J., Bradfield, C. A., and Mezrich, J. D.  The Aryl Hydrocarbon Receptor Influences Transplant Outcomes in Response to Environmental Signals.  Toxicol. Environ. Chem., 94:  1175-1187, 2012.

Siddens, L. K., Larkin, A., Krueger, S. K., Bradfield, C. A., Waters, K. M., Tilton, S. C., Pereira, C. B., Löhr, C. V., Arlt, V. M., Phillips, D. H., Williams, D. E., and Baird, W. M.  Polycyclic Aromatic Hydrocarbons as Skin Carcinogens:  Comparison of Benzo[a]pyrene, Dibenzo[def,p]chrysene and Three Environmental Mixtures in the FVB/N Mouse.  Toxicol. Appl. Pharmacol., 264: 377-386, 2012.

Xing, Y., Nukaya, M., Satyshur, K. A., Jiang, L., Stanevich, V., Korkmaz, E. N., Burdette, L., Kennedy, G. D., Cui, Q., and Bradfield, C. A.  Identification of the Ah-Receptor Structural Determinants for Ligand Preferences.  Toxicol. Sci., 129: 86-97, 2012.

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