UW madison
UW School of Medicine and Public Health
Carbone Cancer Center

Christopher A. Bradfield, Ph.D.

Christopher Bradfield
Professor of Oncology
Genetics Program Member - UW Carbone Cancer Center

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

213A McArdle Lab Bldg
Office - (608) 262-2024; Lab (608) 262-1209
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: 


Cedernaes J, Huang W, Ramsey KM, Waldeck N, Cheng L, Marcheva B, Omura C, Kobayashi Y, Peek CB, Levine DC, Dhir R, Awatramani R, Bradfield CA, Wang XA, Takahashi JS, Mokadem M, Ahima RS, Bass J. Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron. Cell Metab. 2019 May 7;29(5):1078-1091.e5. doi: 10.1016/j.cmet.2019.01.023. Epub 2019 Feb 28. PubMed PMID: 30827863; PubMed Central PMCID: PMC6506361.

Mescher M, Tigges J, Rolfes KM, Shen AL, Yee JS, Vogeley C, Krutmann J, Bradfield CA, Lang D, Haarmann-Stemmann T. The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver. Arch Toxicol. 2019 Jul;93(7):1917-1926. doi: 10.1007/s00204-019-02488-5. Epub 2019 May 20. PubMed PMID: 31111189.

O'Driscoll CA, Owens LA, Hoffmann EJ, Gallo ME, Afrazi A, Han M, Fechner JH, Schauer JJ, Bradfield CA, Mezrich JD. Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE. Environ Res. 2019 Jan;168:178-192. doi: 10.1016/j.envres.2018.09.038. Epub 2018 Oct 1. PubMed PMID: 30316103; PubMed Central PMCID: PMC6263800.

Terry MB, Michels KB, Brody JG, Byrne C, Chen S, Jerry DJ, Malecki KMC, Martin MB, Miller RL, Neuhausen SL, Silk K, Trentham-Dietz A; Breast Cancer and the Environment Research Program (BCERP). Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research. Breast Cancer Res. 2019 Aug 20;21(1):96. doi: 10.1186/s13058-019-1168-2. Review. PubMed PMID: 31429809; PubMed Central PMCID: PMC6701090.


Clements J, Sanchez-Sedillo B, Bradfield CA, Groves RL. Transcriptomic analysis reveals similarities in genetic activation of detoxification mechanisms resulting from imidacloprid and chlorothalonil exposure. PLoS One. 2018 Oct 25;13(10):e0205881. doi: 10.1371/journal.pone.0205881. eCollection 2018. PubMed PMID: 30359414; PubMed Central PMCID: PMC6201883.

Clements J, Schoville S, Clements A, Amezian D, Davis T, Sanchez-Sedillo B, Bradfield C, Huseth AS, Groves RL. Agricultural fungicides inadvertently influence the fitness of Colorado potato beetles, Leptinotarsa decemlineata, and their susceptibility to insecticides. Sci Rep. 2018 Sep 5;8(1):13282. doi: 10.1038/s41598-018-31663-4. PubMed PMID: 30185821; PubMed Central PMCID: PMC6125405.

Nikodemova M, Yee J, Carney PR, Bradfield CA, Malecki KM. Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures. Environ Int. 2018 Apr;113:249-258. doi: 10.1016/j.envint.2018.02.016. Epub 2018 Feb 16. PubMed PMID: 29459183; PubMed Central PMCID: PMC5866236.

O'Driscoll CA, Gallo ME, Hoffmann EJ, Fechner JH, Schauer JJ, Bradfield CA, Mezrich JD. Polycyclic aromatic hydrocarbons (PAHs) present in ambient urban dust drive proinflammatory T cell and dendritic cell responses via the aryl hydrocarbon receptor (AHR) in vitro. PLoS One. 2018 Dec 21;13(12):e0209690. doi: 10.1371/journal.pone.0209690. eCollection 2018. PubMed PMID: 30576387; PubMed Central PMCID: PMC6303068

O'Driscoll CA, Owens LA, Gallo ME, Hoffmann EJ, Afrazi A, Han M, Fechner JH, Schauer JJ, Bradfield CA, Mezrich JD. Differential effects of diesel exhaust particles on T cell differentiation and autoimmune disease. Part Fibre Toxicol. 2018 Aug 24;15(1):35. doi: 10.1186/s12989-018-0271-3. PubMed PMID: 30143013; PubMed Central PMCID: PMC6109291.

Seok SH, Ma ZX, Feltenberger JB, Chen H, Chen H, Scarlett C, Lin Z, Satyshur KA, Cortopassi M, Jefcoate CR, Ge Y, Tang W, Bradfield CA, Xing Y. Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR). J Biol Chem. 2018 Feb 9;293(6):1994-2005. doi: 10.1074/jbc.RA117.000631. Epub 2017 Dec 26. PubMed PMID: 29279331; PubMed Central PMCID: PMC5808761.


Seok SH, Lee W, Jiang L, Molugu K, Zheng A, Li Y, Park S, Bradfield CA, Xing Y. Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex. Proc Natl Acad Sci U S A. 2017 May 23;114(21):5431-5436. doi: 10.1073/pnas.1617035114. Epub 2017 Apr 10. PubMed PMID: 28396409; PubMed Central PMCID: PMC5448172.

Shen AL, Moran SM, Glover EA, Teixeira LB, Bradfield CA. Retinal pathology in the PPCD1 mouse. PLoS One. 2017 Oct 5;12(10):e0185094. doi: 10.1371/journal.pone.0185094. eCollection 2017. PubMed PMID: 28981549; PubMed Central PMCID: PMC5628829.

Vaidyanathan B, Chaudhry A, Yewdell WT, Angeletti D, Yen WF, Wheatley AK, Bradfield CA, McDermott AB, Yewdell JW, Rudensky AY, Chaudhuri J. The aryl hydrocarbon receptor controls cell-fate decisions in B cells. J Exp Med. 2017 Jan;214(1):197-208. doi: 10.1084/jem.20160789. PubMed PMID: 28011866; PubMed Central PMCID: PMC5206498.


Díaz-Díaz CJ, Ronnekleiv-Kelly SM, Nukaya M, Geiger PG, Balbo S, Dator R, Megna BW, Carney PR, Bradfield CA, Kennedy GD. The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse. Ann Surg. 2016 Sep;264(3):429-36. doi: 10.1097/SLA.0000000000001874. PubMed PMID: 27433903; PubMed Central PMCID: PMC5125557.

Pan X, Bradfield CA, Hussain MM. Global and hepatocyte-specific ablation of Bmal1 induces hyperlipidaemia and enhances atherosclerosis. Nat Commun. 2016 Oct 10;7:13011. doi: 10.1038/ncomms13011. PubMed PMID: 27721414; PubMed Central PMCID: PMC5062545.

Shen AL, Moran SA, Glover EA, Drinkwater NR, Swearingen RE, Teixeira LB, Bradfield CA. Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression. PLoS One. 2016 Jun 16;11(6):e0157577. doi: 10.1371/journal.pone.0157577. eCollection 2016. PubMed PMID: 27310661; PubMed Central PMCID: PMC4910986.


Perelis M, Marcheva B, Ramsey KM, Schipma MJ, Hutchison AL, Taguchi A, Peek CB, Hong H, Huang W, Omura C, Allred AL, Bradfield CA, Dinner AR, Barish GD, Bass J. Pancreatic β cell enhancers regulate rhythmic transcription of genes controlling insulin secretion. Science. 2015 Nov 6;350(6261):aac4250. doi: 10.1126/science.aac4250. PubMed PMID: 26542580; PubMed Central PMCID: PMC4669216


Izumo, M., Pejchal, M., Schook, A. C., Lange, R. P., Walisser, J. A., Sato, T. R., Wang, X., Bradfield, C. A., and Takahashi, J. S.  Differential Effects of Light and Feeding on Circadian Organization of Peripheral Clocks in a Forebrain Bmal1 Mutant.  eLife, 3:e04617, 2014.

Johnson, B. P., Walisser, J. A., Liu, Y., Shen, A. L., McDearmon, E. L., Moran, S. M., McIntosh, B. E., Vollrath, A. L., Schook, A. C., Takahashi, J. S., and Bradfield, C. A.  Hepatocyte Circadian Clock Controls Acetaminophen Bioactivation through NADPH-Cytochrome P450 Oxidoreductase.  Proc. Natl. Acad. Sci. USA, 111(52):  18757-18762, 2014.

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., 140(1): 135-143, 2014.

Liu, Y., Johnson, B. P., Shen, A. L., Walisser, J. A., Krentz, K. J., Moran, S. M., Sullivan, R., Glover, E., Parlow, A. F., Drinkwater, N. R., Schuler, L. A., and Bradfield, C. A.  Loss of BMAL1 in Ovarian Steroidogenic Cells Results in Implantation Failure in Female Mice.  Proc. Natl. Acad. Sci. USA, 111(39): 14295-14300, 2014.

Sengupta, S., Johnson, B. P., Swanson, S. A., Stewart, R., Bradfield, C. A., and Thomson, J. A.  Aggregate Culture of Human Embryonic Stem Cell-Derived Hepatocytes in Suspension Are an Improved in Vitro Model for Drug Metabolism and Toxicity Testing.  Toxicol. Sci., 140(1): 236-245, 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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