The Murphy laboratory focuses on two tumor suppressor proteins that are commonly mutated in human cancer, p53 and p14ARF. The p53 and p14ARF proteins regulate the processes of cell death (apoptosis) and survival (autophagy), respectively. Apoptosis (programmed cell death) is what Murphy describes as the cell’s most important defense mechanism against cancer, and is kept tightly regulated by p53. In contrast, autophagy (literally, the cell ingesting itself in order to subsist) is a critical survival program for tumor cells. Murphy’s interest is in how genetic variants in the p53 tumor suppressor gene that exist in human populations, called polymorphisms, affect the ability of this protein to induce apoptosis, and hence combat tumor development. Her studies have relevance for understanding inter-individual differences in cancer risk and progression, particularly in ethnic populations where these variants occur with high frequency. A related interest is to target the autophagy pathway for cancer therapy by using small molecule inhibitors of this pathway in order to selectively eradicate tumor cells.

Murphy obtained a bachelors of science degree in biochemistry at Rutgers University, followed by a doctorate in molecular biology at the University of Pennsylvania School of Medicine. In 1994, she began postdoctoral research at Princeton University in the laboratory of Arnold J. Levine, Ph.D., the co-discoverer of p53 and a pioneer in the field of tumor suppressor genes and cancer biology.

In 1998, Murphy became an Assistant Professor at Fox Chase Cancer Center, where she was promoted to Associate Professor in 2003, and Full Professor in 2011. She is also an adjunct professor at Drexel University’s College of Medicine. Since 1999, she has received continuous research support from the National Cancer Institute for her studies. Murphy joined The Wistar Institute’s Molecular and Cellular Oncogenesis Program in 2011.

1 - Azzam GA, Frank AK, Hollstein M, Murphy ME. Tissue-specific apoptotic effects of the p53 codon 72 polymorphism in a mouse model. Cell Cycle, 2011;10(9):1352-5. PMID: 21566457

2 - Feng Z, Zhang C, Kang HJ, Sun Y, Wang H, Naqvi A, Frank AK, Rosenwaks Z, Murphy ME, Levine AJ, Hu W. Regulation of female reproduction by p53 and its family members. FASEB J. 2011 Mar 14. PubMed PMID: 21402718.

3 - Frank AK, Pietsch EC, Dumont P, Tao J, Murphy ME. Wild-type and mutant p53 proteins interact with mitochondrial caspase-3. Cancer Biol Ther. 2011;11(8):740-5. PubMed PMID: 21307660; PubMed Central PMCID: PMC3100564.

4 - Frank, AK, Leu JI, Zhou Y, Devarajan K, Nedelko T, Klein-Szanto A, Hollstein M, Murphy ME. The codon 72 polymorphism of p53 regulates interation with NF-{kappa}B and transactivation of genes involved in immunity and inflammation. Mol Cell Biol. 2011;31(6):1201-13. PubMed PMID: 21245379; PubMed Central PMCID: PMC3067895.

5 - Murphy ME. p53, transcriptional repression, and drug sensitivity: fresh perspectives on an old activity. Cell Cycle. 2010;9(22):4432. PubMed PMID: 21188768.

6 - Balaburski G, Hontz R and Murphy ME. p53 and ARF: Unexpected players in autophagy. Trends in Cell Biology, 2010;20(6):363-9. PubMed PMID: 20303758

7 - Whibley C, Odell AF, Nedelko T, Balaburski G, Murphy M, Liu Z, Stevens L, Walker JH, Routledge M, Hollstein M. Wild-type and Hupki (human p53 knock-in) murine embryonic fibroblasts: p53/ARF pathway disruption in spontaneous escape from senescence. J Biol Chem. 2010;285(15):11326-35. 20118236

8 - Leu JI, Pimkina J, Frank A, Murphy ME, and George DL. A Small Molecule Inhibitor of Inducible Heat Shock Protein 70 (HSP70). Mol Cell36:15-27, 2009. PMID: 19818706

9 - Sykes SM, Stanek TJ, Frank A, Murphy ME, McMahon SB. Acetylation of the DNA binding domain regulates transcription-independent apoptosis by p53. J Biol Chem. 284:20197-205, 2009. PMID: 19494119

10 - Kang HJ, Feng Z, Sun Y, Atwal G, Murphy ME, Rebbeck TR, Rosenwaks Z, Levine AJ, Hu W. Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans. Proc Natl Acad Sci U S A. 2009;106(24):9761-6. PMID: 19470478