Halogenated aromatic hydrocarbons (HAHs) constitute a class of environmental contaminants that includes dioxins and polychlorinated biphenyls (PCBs).  HAHs are widespread and persistent in aquatic habitats, and many fish populations suffer exposure to these potent toxicants.  An important goal of my recent research has been to characterize the interactions between biological molecules that regulate the physiological response of fish to HAH exposure.

    The molecules that make up this signal transduction pathway are increasingly well characterized in mammalian systems.  The hallmark of the pathway is the aryl hydrocarbon (Ah) receptor, a ligand-activated transcription factor.  Certain HAHs bind specifically to the Ah receptor in the cytosol, triggering its translocation to the cell nucleus, where it forms a complex with an additional protein called ARNT (Ah Receptor Nuclear Translocator).  The Ah Receptor:ARNT complex binds to specific sequences (xenobiotic responsive elements or XREs) near the promoters of target genes, altering the rate of messenger RNA synthesis.  The best characterized HAH-responsive gene is Cytochrome P4501A1 (CYP1A1), an enzyme involved in detoxification of certain aryl hydrocarbons.  The presence of CYP1A1 is widely used as an indicator of aryl hydrocarbon exposure in many types of animals.

    The primary animal model in my studies of this system in fish has been the salt marsh fish, Fundulus heteroclitus (Atlantic killifish or mummichog).  This species is remarkable because some chronically exposed populations actually develop resistance to environmental contaminants.  For example, Fundulus from New Bedford Harbor, and EPA Superfund site in southeastern Massachusetts, exhibit heritable resistance to the toxic effects of HAHs.   My efforts to characterize the aryl hydrocarbon signaling mechanisms in F. heteroclitushave focused particular attention on interactions involving components downstream of the Ah receptor itself, including ARNT and the CYP1A promoter.  One purpose of this work is the development of in vitro assays useful for probing individual steps along the pathway for alterations that may underlie the dioxin-resistant phenotype of the New Bedford Harbor population.  These studies have also revealed unexpected insights about the evolution of ARNT proteins in the fish lineage.  Additional ongoing work concerns the evolution and diversity of ARNT proteins in different species of fish and other nonmammalian vertebrates and the relationship between the type, number, and expression patterns of different ARNT isoforms to interspecies variations in HAH toxicity.

    A recently initiated research avenue focuses on the physiological consequences in fish of simultaneous exposure to two environmental stresses:  dioxin-like compounds and oxygen limitation.  Contamination of aquatic habitats by HAHs is a long-standing ecological concern.  Oxygen limitation, related to the eutrophication that results from agricultural runoff and sewage discharge, is emerging as a major problem.  As the incidence of hypoxia increases, HAH contamination and oxygen limitation are likely to impact the same waters, each stress potentially increasing the sensitivity of fish to the other.  These studies utilize molecular and pathological endpoints in Fundulus heteroclitus exposed to both HAHs and oxygen stress to examine this possibility.

RESEARCH SUPPORT:

National Institute of Environmental Health Sciences, National Institutes of Health.
            F32-ES05800        Aryl Hydrocarbon Signal Transduction Mechanisms in Fish

Rinehart Coastal Research Center
           Physiological Consequences of Multiple Environmental Stresses toEstuarineFish:
                Dioxin-like compounds and hypoxia.

Woods Hole Oceanographic Institution Postdoctoral Scholar Program.
            Marine Toxicology Postdoctoral Scholar Fellowship funded by the Donaldson
            Charitable Trust.

EDUCATION:
 

Degree	Year	Institution	Department/Division
Ph.D.*	(1997)	Emory University	Biological and Biomedical Sciences
M.S.	(1991)	East Tennessee State University	Biological Sciences
B.S.	(1987)	Davidson College	Biology

*Click here for summary of PhD thesis.

PUBLICATIONS:

Powell, W. H., R. Bright, S. M. Bello, and M. E. Hahn (2000)  Developmental and tissue-specific expression of AHR1, AHR2, and ARNT2 in dioxin-sensitive and -resistant populations of the marine fish, Fundulus heteroclitus.  Tox. Sci., accepted pending minor revision.

Powell, W. H. and M. E. Hahn. (2000)  Evolution of aryl hydrocarbon signaling proteins:  Diversity of ARNT isoforms in fish, Mar. Env. Res.,  in press.

Karchner, S.I., W. H. Powell, and M. E. Hahn (1999)  Identification and functional characterization of two divergent aryl hydrocarbon receptors in the teleost Fundulus heteroclitus:  Evidence for a novel subfamily of ligand-binding bHLH-PAS factors.  J. Biol. Chem. 274(47):33814-33824.

Powell, W. H., S. I. Karchner, R. Bright, and M. E. Hahn. (1999)  Functional diversity of vertebrate ARNT proteins:  Identification of ARNT2 as the predominant form of ARNT in the marine teleost, Fundulus heteroclitus.  Arch. Biochem. Biophys. 361(1):156-163..

Powell, W., J. C. Lennon, P. Elsevier, and D. Reines.  (1997)  Glutamic acid-371 of the barnase homology domain in RNA polymerase II is not required for SII-activated RNA cleavage.  Mol. Gen. Genet.  253(4):507-511.

Powell, W., B. Bartholomew, and D. Reines.  (1996)  Elongation factor SII contacts the 3' end of RNA in the RNA polymerase II elongation complex.  J. Biol. Chem.  271:22301-22304.

Powell, W. and D. Reines.  (1996)  Mutations in the second largest subunit of RNA polymerase II cause 6-azauracil sensitivity in yeast and increased transcriptional arrest in vitro.  J. Biol. Chem.  271:6866-6873.

Conaway, R. C., D. Reines, K. P. Garrett, W. Powell, and J. W. Conaway.  (1996)  Purification of RNA polymerase II general transcription factors from rat liver.  Meth. Enzymol.  273:194-207.

Gu, W., W. Powell, J. Mote, Jr., and D. Reines.  (1993)  Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA.  J. Biol. Chem.  268:25604-25616.

Reines, D., P. Ghanouni, W. Gu, J. Mote, Jr., and W. Powell.  (1993)  Transcription elongation by RNA polymerase II:  Mechanisms of SII activation.  Cell. Mol. Biol. Res.  39:331-338.

Powell, W. H. and H. A. Miller III.  (1992)  Dexamethasone stimulates release of an ANP-like substance from rainbow trout cardiocytes.  Am. J. Physiol.  263:R447-R451.

ABSTRACTS/PRESENTATIONS:

Powell, W. H., S. I. Karchner, R. Bright, and M. E. Hahn.  Aryl hydrocarbon signaling mechanisms in fish:  ARNT2 is the predominant form of ARNT in Fundulus heteroclitus.  Tenth International Symposium on Pollutant Responses in Marine Organisms (PRIMO 10)  Williamsburg, VA  April, 1999.

Karchner, S. I., W. H. Powell, and M. E. Hahn.  Tenth International Symposium on Pollutant Responses in Marine Organisms (PRIMO 10)  Williamsburg, VA  April, 1999.

Powell, W. H., S. I. Karchner, R. Bright, and M. E. Hahn.  Functional diversity of vertebrate ARNT proteins:  Identification of ARNT2 as the predominant form of ARNT in the marine fish, Fundulus heteroclitus.  Society of Toxicology, New Orlearns, LA  March, 1999.

Karchner, S. I., W. H. Powell, and M. E. Hahn. Society of Toxicology, New Orlearns, LA  March, 1999.

Powell, W. H., S. I. Karchner, and M. E. Hahn.  Aryl hydrocarbon signaling components in Fundulus heteroclitus:  A phylogenetic perspective.  Society for Environmental Toxicology and Chemistry, Charlotte, NC  November, 1998.

Powell, W. H., H. G. Morrison, E. J. Weil, S. I. Karchner, M. L. Sogin, M. E. Hahn, J. J. Stegeman.  Cloning of cDNA and promoter sequences of Cytochrome P4501A from killifish (Fundulus heteroclitus).  Society for Environmental Toxicology and Chemistry, Charlotte, NC  November, 1998.

Powell, W.H.  Aryl hydrocarbon signal transduction in fish: In vitro assay development yields evolutionary insights.  NUTMEG (New England Membrane Enzymes Group) Meeting, Brownsville, VT  October, 1998.

Karchner, S.I., W.H. Powell and M. E. Hahn.  Two Ah receptors in the marine fish, Fundulus heteroclitus:  TCDD binding and tissue-specific expression.   NUTMEG (New England Membrane Enzymes Group) Meeting, Brownsville, VT  October, 1998.

Black, V.H., S.I. Karchner, W. Powell, and M. Hahn.  Differential expression of CYP1A1 and CYP1A2, but not of AHR and ARNT, in guinea pig liver and adrenal.  NUTMEG (New England Membrane Enzymes Group) Meeting, Brownsville, VT  October, 1998.

Powell, W. H., S. I. Karchner, and M. E. Hahn.  Aryl hydrocarbon signaling components in Fundulus heteroclitus:  A phylogenetic perspective.  National Institute of Environmental Health Sciences Workshop on Unique Marine/Freshwater Models for Environmental Health Research, Research Triangle Park, NC  April, 1998.

Powell, W. H. and M. E. Hahn.  An ARNT2 homolog is expressed in the liver of the killifish (Fundulus heteroclitus). NUTMEG (New England Membrane Enzymes Group) Meeting, Brownsville, VT  October, 1997.

Powell, W., J. C. Lennon, and D. Reines.  Mutations in the second largest subunit of RNA polymerase II cause 6-azauracil sensitivity in yeast and in vitro transcriptional defects.  Keystone symposium on Transcription Mechanisms, Taos, NM  March, 1996.

Powell, W. H. and H. A. Miller III.  Dexamethasone stimulates release of an ANP-like substance from rainbow trout cardiocytes.  American Society of Cell Biology, San Diego, CA  December, 1990.

Fundulus heteroclitus

Wade H. Powell
Biology Department
Woods Hole Oceanographic Institution
MS #32, Redfield 3-04
Woods Hole, MA  02543

Tel/voice mail:  508-289-3212
Fax:  508-457-2134
email:   wpowell@whoi.edu
 

[Last updated June 9, 2000]