Patrick J.M. Murphy, PhD

Areas of Interest

Molecular chaperone actions in cancer and cardiovascular disease. Pharmacogenetics of heat shock proteins and their use as biomarkers. Impact of commercializing academic research on vulnerable populations. Misuse and abuse of over-the-counter pharmaceuticals by adolescents.

Recent Publications

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.

Scholarly Activities

 

Dedomenico 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.