ZFIN Lab: Stegeman Lab

ZFIN ID: ZDB-LAB-160308-3

Stegeman Lab

PI/Director:	Stegeman, John J.
Co-PI / Senior Researcher:	Goldstone, Jed
Contact Person:	Goldstone, Jed
Email:	jgoldstone@whoi.edu
URL:	https://www2.whoi.edu/site/stegemanlab/
Address:	Biology Department Woods Hole Oceanographic Institution 266 Woods Hole Rd. MS#32 Woods Hole, MA 02543
Country:	United States
Phone:	508-289-2368
Fax:	508-457-2134
Line Designation:	wh

GENOMIC FEATURES ORIGINATING FROM THIS LAB

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STATEMENT OF RESEARCH INTERESTS

Our research focuses on the biochemistry, evolution, and regulation of cytochrome P450 enzymes and their roles in biochemical toxicology. We are interested in the metabolism and biological effects of xenobiotics including in particular PCBs, and natural products, in aquatic animals. We investigate how the structure-function relationships involved in the effects of these chemicals are related to the susceptibility of developing animals. We are also interested in the developmental neurotoxicity of legacy and emerging contaminants.

LAB MEMBERS

Brun, Nadja Post-Doc

ZEBRAFISH PUBLICATIONS OF LAB MEMBERS

Brun, N.R., Salanga, M.C., Mora-Zamorano, F.X., Lamb, D.C., Goldstone, J.V., Stegeman, J.J. (2021) Orphan cytochrome P450 20a1 CRISPR/Cas9 mutants and neurobehavioral phenotypes in zebrafish. Scientific Reports. 11:23892

Brun, N.R., Panlilio, J.M., Zhang, K., Zhao, Y., Ivashkin, E., Stegeman, J.J., Goldstone, J.V. (2021) Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish. Communications biology. 4:1129

Eide, M., Zhang, X., Karlsen, O.A., Goldstone, J.V., Stegeman, J., Jonassen, I., Goksøyr, A. (2021) The chemical defensome of five model teleost fish. Scientific Reports. 11:10546

Zhang, K., Liang, J., Brun, N.R., Zhao, Y., Werdich, A.A. (2021) Rapid Zebrafish Behavioral Profiling Assay Accelerates the Identification of Environmental Neurodevelopmental Toxicants. Environmental science & technology. 55(3):1919-1929

Salanga, M.C., Brun, N.R., Francolini, R.D., Stegeman, J.J., Goldstone, J.V. (2019) CRISPR-Cas9 mutated pregnane x receptor (pxr) retains pregnenolone-induced expression of cyp3a65 in zebrafish (Danio rerio) larvae. Toxicological sciences : an official journal of the Society of Toxicology. 174(1):51-62

Lille-Langøy, R., Karlsen, O.A., Myklebust, L.M., Goldstone, J.V., Mork-Jansson, A., Male, R., Blumberg, B., Stegeman, J.J., Goksøyr, A. (2018) Sequence variations in pxr (nr1i2) from zebrafish (Danio rerio) strains affect nuclear receptor function. Toxicological sciences : an official journal of the Society of Toxicology. 168(1):28-39

Holland, E.B., Goldstone, J.V., Pessah, I.N., Whitehead, A., Reid, N.M., Karchner, S.I., Hahn, M.E., Nacci, D.E., Clark, B.W., Stegeman, J.J. (2017) Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus): A phylogenetic and population-based comparison. Aquatic toxicology (Amsterdam, Netherlands). 192:105-115

Sant, K.E., Hansen, J.M., Williams, L.M., Tran, N.L., Goldstone, J.V., Stegeman, J.J., Hahn, M.E., Timme-Laragy, A. (2017) The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo. Redox Biology. 13:207-218

Tokunaga, S., Woodin, B.R., Stegeman, J.J. (2016) Plant lignan secoisolariciresinol suppresses pericardial edema caused by dioxin-like compounds in developing zebrafish: Implications for suppression of morphological abnormalities. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 96:160-6

Wincent, E., Kubota, A., Timme-Laragy, A., Jönsson, M.E., Hahn, M.E., Stegeman, J.J. (2016) Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochemical pharmacology. 110-111:117-29

Lemaire, B., Kubota, A., O'Meara, C.M., Lamb, D.C., Tanguay, R.L., Goldstone, J.V., Stegeman, J.J. (2016) Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders. Toxicology and applied pharmacology. 296:73-84

Hahn, M.E., Timme-Laragy, A.R., Karchner, S.I., Stegeman, J.J. (2015) Nrf2 and Nrf2-related proteins in development and developmental toxicity:Insights from studies in zebrafish (danio rerio). Free radical biology & medicine. 88(Pt B):275-89

Stegeman, J.J., Behrendt, L., Woodin, B.R., Kubota, A., Lemaire, B., Pompon, D., Goldstone, J.V., Urban, P. (2015) Functional Characterization of Zebrafish Cytochrome P450 1 Family Proteins Expressed in Yeast. Biochimica et biophysica acta. General subjects. 1850(11):2340-52

Wincent, E., Stegeman, J.J., Jönsson, M.E. (2015) Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions. Toxicology and applied pharmacology. 284(2):163-79

Kubota, A., Goldstone, J.V., Lemaire, B., Takata, M., Woodin, B.R., Stegeman, J.J. (2015) Pregnane X Receptor and Aryl Hydrocarbon Receptor Both Are Involved in Transcriptional Regulation of pxr, CYP2 and CYP3 Genes in Developing Zebrafish. Toxicological sciences : an official journal of the Society of Toxicology. 143(2):398-407

Hahn, M.E., McArthur, A.G., Karchner, S.I., Franks, D.G., Jenny, M.J., Timme-Laragy, A.R., Stegeman, J.J., Woodin, B.R., Cipriano, M.J., Linney, E. (2014) The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. PLoS One. 9:e113158

Teraoka, H., Okuno, Y., Nijoukubo, D., Yamakoshi, A., Peterson, R.E., Stegeman, J.J., Kitazawa, T., Hiraga, T., Kubota, A. (2014) Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 154C:19-26

Morrison, A.M., Goldstone, J.V., Lamb, D.C., Kubota, A., Lemaire, B., and Stegeman, J.J. (2014) Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14α-demethylase. Biochimica et biophysica acta. General subjects. 1840(6):1825-36

Timme-Laragy, A.R., Goldstone, J.V., Imhoff, B.R., Stegeman, J.J., Hahn, M.E., and Hansen, J.M. (2013) Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo. Free radical biology & medicine. 65:89-101

Williams, L.M., Timme-Laragy, A.R., Goldstone, J.V., McArthur, A.G., Stegeman, J.J., Smolowitz, R.M., and Hahn, M.E. (2013) Developmental expression of the Nfe2-related factor (Nrf) transcription factor family in the zebrafish, Danio rerio. PLoS One. 8(10):e79574

Bainy, A.C., Kubota, A., Goldstone, J.V., Lille-Langøy, R., Karchner, S.I., Celander, M.C., Hahn, M.E., Goksøyr, A., and Stegeman, J.J. (2013) Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in Zebrafish (Danio rerio). Aquatic toxicology (Amsterdam, Netherlands). 142-143:447-457

Kubota, A., Bainy, A.C., Woodin, B.R., Goldstone, J.V., and Stegeman, J.J. (2013) The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): Expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers. Toxicology and applied pharmacology. 272(1):172-9

Amemiya, C.T., Alfoldi, J., Lee, A.P., Fan, S., Philippe, H., MacCallum, I., Braasch, I., Manousaki, T., Schneider, I., Rohner, N., Organ, C., Chalopin, D., Smith, J.J., Robinson, M., Dorrington, R.A., Gerdol, M., Aken, B., Biscotti, M.A., Barucca, M., Baurain, D., Berlin, A.M., Blatch, G.L., Buonocore, F., Burmester, T., Campbell, M.S., Canapa, A., Cannon, J.P., Christoffels, A., de Moro, G., Edkins, A.L., Fan, L., Fausto, A.M., Feiner, N., Forconi, M., Gamieldien, J., Gnerre, S., Gnirke, A., Goldstone, J.V., Haerty, W., Hahn, M.E., Hesse, U., Hoffmann, S., Johnson, J., Karchner, S.I., Karaku, S., Lara, M., Levin, J.Z., Litman, G.W., Mauceli, E., Miyake, T., Mueller, M.G., Nelson, D.R., Nitsche, A., Olmo, E., Ota, T., Pallavicini, A., Panji, S., Picone, B., Ponting, C.P., Prohaska, S.J., Przybylski, D., Saha, N.R., Ravi, V., Ribeiro, F.J., Sauka-Spengler, T., Scapigliati, G., Searle, S.M.J., Sharpe, T., Simakov, O., Stadler, P.F., Stegeman, J.J., Sumiyama, K., Tabbaa, D., Tafer, H., Turner-Maier, J., van Heusden, P., White, S., Williams, L., Yandell, M., Brinkmann, H., Volff, J.N., Tabin, C.J., Shubin, N., Schartl, M., Jaffe, D.B., Postlethwait, J.H., Venkatesh, B., Palma, F.D., Lander, E.S., Meyer, A., and Lindblad-Toh, K. (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature. 496:311-316

Jönsson, M.E., Kubota, A., Timme-Laragy, A., Woodin, B., and Stegeman, J.J. (2012) Ahr2-dependance of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish. Toxicology and applied pharmacology. 265(2):166-174

Goldstone, H.M., Tokunaga, S., Schlezinger, J.J., Goldstone, J.V., and Stegeman, J.J. (2012) EZR1: A Novel Family of Highly Expressed Retroelements Induced by TCDD and Regulated by a NF-kappaB-Like Factor in Embryos of Zebrafish (Danio rerio). Zebrafish. 9(1):15-25

Timme-Laragy, A.R., Karchner, S.I., Franks, D.G., Jenny, M.J., Harbeitner, R.C., Goldstone, J.V., McArthur, A.G., and Hahn, M.E. (2012) Nrf2b: novel zebrafish paralog of the oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2). The Journal of biological chemistry. 287(7):4609-4627

Goldstone, J.V., and Stegeman, J.J. (2012) Methodological approaches to cytochrome p450 profiling in embryos. Methods in molecular biology (Clifton, N.J.). 889:265-275

Kubota, A., Stegeman, J.J., Woodin, B.R., Iwanaga, T., Harano, R., Peterson, R.E., Hiraga, T., and Teraoka, H. (2011) Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2. Toxicology and applied pharmacology. 253(3):244-52

Celander, M.C., Goldstone, J.V., Denslow, N.D., Iguchi, T., Kille, P., Meyerhoff, R.D., Smith, B.A., Hutchinson, T.H., and Wheeler, J.R. (2011) Species extrapolation for the 21st century. Environmental toxicology and chemistry. 30(1):52-63

Jönsson, M.E., Woodin, B.R., Stegeman, J.J., and Brunström, B. (2011) Cytochrome p450 1 genes in birds: evolutionary relationships and transcription profiles in chicken and Japanese quail embryos. PLoS One. 6(12):e28257

Goldstone, J.V., McArthur, A.G., Kubota, A., Zanette, J., Parente, T., Jonsson, M.E., Nelson, D.R., and Stegeman, J.J. (2010) Identification and developmental expression of the full complement of cytochrome P450 genes in zebrafish. BMC Genomics. 11:643

Teraoka, H., Ogawa, A., Kubota, A., Stegeman, J.J., Peterson, R.E., and Hiraga, T. (2010) Malformation of certain brain blood vessels caused by TCDD activation of Ahr2/Arnt1 signaling in developing zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 99(2):241-247

Behrendt, L., Jönsson, M.E., Goldstone, J.V., and Stegeman, J.J. (2010) Induction of cytochrome P450 1 genes and stress response genes in developing zebrafish exposed to ultraviolet radiation. Aquatic toxicology (Amsterdam, Netherlands). 98(1):74-82

Jönsson, M.E., Franks, D.G., Woodin, B.R., Jenny, M.J., Garrick, R.A., Behrendt, L., Hahn, M.E., and Stegeman, J.J. (2009) The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) binds multiple AHRs and induces multiple CYP1 genes via AHR2 in zebrafish. Chemico-biological interactions. 181(3):447-454

Jenny, M.J., Karchner, S., Franks, D., Woodin, B.W., Stegeman, J.J., and Hahn, M.E. (2009) Distinct roles of two zebrafish AHR repressors (AHRRa and AHRRb) in embryonic development and regulating the response to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Toxicological sciences : an official journal of the Society of Toxicology. 110(2):426-441

Goldstone, J.V., Jönsson, M.E., Behrendt, L., Woodin, B.R., Jenny, M.J., Nelson, D.R., and Stegeman, J.J. (2009) Cytochrome P450 1D1: A novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD. Archives of biochemistry and biophysics. 482(1-2):7-16

Goldstone, J.V., and Stegeman, J.J. (2008) Gene structure of the novel cytochrome P4501D1 genes in stickleback (Gasterosteus aculeatus) and medaka (Oryzias latipes). Marine Environmental Research. 66(1):19-20

Goldstone, J.V., Goldstone, H.M., Morrison, A.M., Tarrant, A., Kern, S.E., Woodin, B.R., and Stegeman, J.J. (2007) Cytochrome P450 1 genes in early deuterostomes (tunicates and sea urchins) and vertebrates (chicken and frog): origin and diversification of the CYP1 gene family. Mol. Biol. Evol.. 24(12):2619-2631

Jönsson, M.E., Jenny, M.J., Woodin, B.R., Hahn, M.E., and Stegeman, J.J. (2007) Role of AHR2 in the Expression of Novel Cytochrome P450 1 Family Genes, Cell Cycle Genes, and Morphological Defects in Developing Zebrafish Exposed to 3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicological sciences : an official journal of the Society of Toxicology. 100(1):180-193

Jonsson, M.E., Orrego, R., Woodin, B.R., Goldstone, J.V., and Stegeman, J.J. (2007) Basal and 3,3',4,4',5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish. Toxicology and applied pharmacology. 221(1):29-41

Dong, W., Muramoto, W., Nagai, Y., Takehana, K., Stegeman, J.J., Teraoka, H., and Hiraga, T. (2006) Retinal Neuronal Cell is a Toxicological Target of Tributyltin in Developing Zebrafish. The Journal of veterinary medical science. 68(6):573-579

Teraoka, H., Urakawa, S., Nanba, S., Nagai, Y., Dong, W., Imagawa, T., Tanguay, R.L., Svoboda, K., Handley-Goldstone, H.M., Stegeman, J.J., and Hiraga, T. (2006) Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions. Toxicology and applied pharmacology. 212(1):24-34

Goldstone, H.M., and Stegeman, J.J. (2006) Molecular mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin cardiovascular embryotoxicity. Drug Metabolism Reviews. 38(1-2):261-289

Godard, C.A., Goldstone, J.V., Said, M.R., Dickerson, R.L., Woodin, B.R., and Stegeman, J.J. (2005) The new vertebrate CYP1C family: Cloning of new subfamily members and phylogenetic analysis. Biochemical and Biophysical Research Communications. 331(4):1016-1024

Handley-Goldstone, H.M., Grow, M.W., and Stegeman, J.J. (2005) Cardiovascular gene expression profiles of dioxin exposure in zebrafish embryos. Toxicological sciences : an official journal of the Society of Toxicology. 85(1):683-693

Zodrow, J.M., Stegeman, J.J., and Tanguay, R.L. (2004) Histological analysis of acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish. Aquatic toxicology (Amsterdam, Netherlands). 66(1):25-38

Dong, W., Teraoka, H., Tsujimoto, Y., Stegeman, J.J., and Hiraga, T. (2004) Role of aryl hydrocarbon receptor in mesencephalic circulation failure and apoptosis in zebrafish embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicological sciences : an official journal of the Society of Toxicology. 77(1):109-116

Prasch, A.L., Teraoka, H., Carney, S.A., Dong, W., Hiraga, T., Stegeman, J.J., Heideman, W., and Peterson, R.E. (2003) Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish. Toxicological sciences : an official journal of the Society of Toxicology. 76(1):138-150

Teraoka, H., Dong, W., Tsujimoto, Y., Iwasa, H., Endoh, D., Ueno, N., Stegeman, J.J., Peterson, R.E., and Hiraga, T. (2003) Induction of cytochrome P450 1A is required for circulation failure and edema by 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish. Biochemical and Biophysical Research Communications. 304(2):223-228

Dong, W., Teraoka, H., Yamazaki, K., Tsukiyama, S., Imani, S., Imagawa, T., Stegeman, J.J., Peterson, R.E., and Hiraga, T. (2002) 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo: local circulation failure in the dorsal midbrain is associated with increased apoptosis. Toxicological sciences : an official journal of the Society of Toxicology. 69(1):191-201

Yamazaki, K., Teraoka, H., Dong, W., Stegeman, J.J., and Hiraga, T. (2002) cDNA cloning and expressions of cytochrome P450 1A in zebrafish embryos. The Journal of veterinary medical science. 64(9):829-833

Godard, C.A., Leaver, M.J., Said, M.R., Dickerson, R.L., George, S., and Stegeman, J.J. (2000) Identification of cytochrome P450 1B-like sequences in two teleost fish species (scup, Stenotomus chrysops and plaice, Pleuronectes platessa) and in a cetacean (striped dolphin, Stenella coeruleoalba). Marine Environmental Research. 50(1-5):7-10

Mizell, M., Romig, E., Stegeman, J., Smolowitz, R., and Katayani-R (1996) Zebrafish embryo monitoring of the aquatic environment: dose-response synergism revealed in combinations of pollutant chemical mixtures. The Biological bulletin. 191(2):292-294

Mizell, M., Stegeman, J.J., Romig, E., Smolowitz, R., Schlezinger, J., Katayani, R., Woodin, B., and Mortensen, M. (1996) Chemically induced cardiovascular defects in developmental states of vertebrates: dose-response and phenotypic comparisons in medaka and zebrafish exposed to aryl hydrocarbon receptor agonists. The Biological bulletin. 191(2):294-295

Mizell, M., Stegeman, J.J., Romig, E., Smolowitz, R., Schlezinger, J., Katayani, R., Woodin, B., Mortensen, M. (1996) Chemically Induced Cardiovascular Defects in Developmental Stages of Vertebrates: Dose-Response and Phenotypic Comparisons in Medaka and Zebrafish Exposed to Aryl Hydrocarbon Receptor Agonists. The Biological bulletin. 191:294-295