Hollie Swanson, Ph.D.
Assistant Professor
Pharmacology
Phone:
(859) 323-1463
Fax:
(859) 323-1981
E-mail:
hswan@uky.edu
Web Page:
http://www.mc.uky.edu/pharmacology/
pharmacology.html
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Research Interests
Our laboratory is focused on study of
the aryl hydrocarbon receptor (AHR) signaling pathway and its role in
altering cell fate. The AHR is a basic helix-loop-helix transcription
factor that binds toxic compounds such as dioxins. These compounds are
pervasive environmental contaminants that are formed during combustion
reactions and certain manufacturing processes. While the endogenous ligand
for the AHR is not known, the best known AHR agonist is dioxin. One of the
long term goals of our research program is determining the mechanisms by
which dioxin, via activation of the AHR, results in tumor promotion.
Known genes that are regulated by the AHR include cytochrome
P4501A1, however, we are also identifying novel, AHR regulated genes. To
understand what genes the AHR regulates under normal conditions and how
these genes are altered during dioxin-induced tumor promotion we are using
cultured human keratinocytes and keratinocytes obtained from mice that
lack the AHR. We have recently discovered that dioxin, via the AHR,
downregulates major regulators of the senescence pathway, p53 and
p16INK4a, block senescence and extends the mortality of these cells.
A second project focuses on determing the role of the AHR in
protecting the cell from apoptosis.
Our laboratory uses a number of
molecular techniques such as gel shift assays, transient transfections,
RNase protection assays, real time RT-PCR, DNA microarray analysis and
chromatin immunoprecipitation assays to address these research questions.
Research Publications/Presentations
Heid,
S.E., Walker, M.K. and Swanson,
H.I. Correlation of cardiotoxicity mediated by halogenated aromatic
hydrocarbons to aryl hydrocarbon receptor activation. Toxicological
Sci. 61, 187-196 (2001).
Swanson, H.I. DNA binding and protein interactions of the AHR
heterodimer that facilitate gene activation.
Chem-Biol Interactions 141, 63-76 (2002).
Swanson, H.I., Whitelaw, M.L., Petrulis, J. R. and Perdew, G.H.
(2002) Use of 4'[125I] Iodoflavone as a tool to characterize ligand
dependent differences in Ah receptor behavior.
J. Biochem. Mol. Tox.
16, 298-310.
Ray, S. and Swanson,
H.I. (2003) Alteration of keratinocyte differentiation and senescence by
the tumor promoter, dioxin. Toxicol
Appl Pharmacol, 192, 131-145.
Ray, S and Swanson, H.I.(2004) Dioxin-induced
immortalization of normal human keratinocytes and silencing of p53 and
p16INK4a. J. Biol. Chem 279,
27187-27193.
Swanson,
H.I. (2004) Cytochrome P450 expression in human keratinocytes:
An aryl hydrocarbon receptor perspective.
Chem. Biol. Interaction (In press).
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