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recent
publications
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Murphy
PJM. 2005. Regulation of glucocorticoid receptor steroid binding
and trafficking by the hsp90/hsp70-based chaperone machinery: Implications
for clinical intervention. Leukemia 19: 710-712.
Murphy
PJM, Morishima Y, Kovacs JJ, Yao TP, and Pratt WB. 2005. Regulation
of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation
of the chaperone. Journal of Biological Chemistry 208: 33792-33799.
Pratt WB, Morishima Y, Murphy PJM, and Harrell JM. 2005. Chaperoning
of glucocorticoid receptors. In: Molecular Chaperones in Health
and Disease. ed. by Gaestel M. Handbook of Experimental Pharmacology.
Heidelberg: Springer-Verlag. pp. 111-138.
Murphy
PJM, Galigniana MD, Morishima Y, Harrell JM, Kwok PRS, Ljungman
M, and Pratt WB. 2004. Pifithrin-a inhibits p53 signaling after
interaction of the tumor suppressor protein with hsp90 and nuclear
translocation. Journal of Biological Chemistry 279: 30195-30201.
Pratt WB, Galigniana MD, Morishima Y, and Murphy PJM. 2004. Role
of molecular chaperones in steroid receptor action. In: The Nuclear
Receptor Superfamily. ed. by McEwan IJ. Volume 40 of Essays in Biochemistry.
London: Portland Press. pp. 41-58.
Murphy,
PJM, Morishima Y, Chen H, Galigniana MD, and Pratt WB. 2003. Visualization
and mechanism of assembly of a glucocorticoid receptor•hsp70 complex
that is primed for subsequent hsp90 dependent opening of the steroid
binding cleft. Journal of Biological Chemistry 278: 34764-34773.
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scholarly
activities
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DeDominico
Scholar-in-Residence, Hope Heart Institute
I
am investigating the pharmacogenetics of molecular chaperone protein
expression and stress-mediated induction in cardiovascular disease.
Molecular chaperones (also referred to as heat shock proteins) are
cellular components that play essential roles in facilitating intracellular
signaling and in assisting the patient respond to environmental
stress. Pharmacogenetics is the study of genetic variability within
a population, which gives rise to differences in drug response from
patient to patient.
Understanding
-- and ultimately accounting for -- interpatient variability in
response to drug therapy is a crucial mechanism for improving patient
care. In conjunction with ongoing clinical trials at the Hope Heart
Institute, we are beginning to establish the extent to which molecular
chaperone expression provides a prognostic value for patients being
treated for cardiovascular disease.
Visiting Scientist, Fred Hutchinson
Cancer Research Center
In
collaboration with faculty in the Human Biology and Basic Sciences
Divisions of the Fred Hutchinson Cancer Research Center, we are
utilizing a novel screening assay to delineate drug sensitivity
of laboratory-derived and naturally occurring strains of yeast.
Yeast serve as a useful model organism that can provide us with
valuable information to better understand disease states, such as
ovarian cancer. By using strains from evolutionary disparate sources,
we are able to explore the extent to which sensitivity to a commonly
used anti-cancer chemotherapeutic is controlled by an individual
gene or gene network.
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