Our Science

Maureen Murphy, Ph.D.

Maureen Murphy, Ph.D.

  • Professor and Program Leader, Molecular and Cellular Oncogenesis Program
  • Associate Vice President for Faculty Affairs
  • Associate Director of Faculty Development
  • Associate Director for Education
  • 215-495-6870, Office
Summary

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; this process 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 in apoptosis and p53 relates to how genetic polymorphisms in the p53 tumor suppressor gene that are more common in African Americans affect the ability of this protein to induce apoptosis and growth arrest, and hence combat tumor development. Her studies have relevance for understanding inter-individual differences in cancer risk and therapy, particularly in ethnic populations where these variants occur with high frequency. With regard to autophagy, Murphy proposes to target the autophagy pathway for cancer therapy by using small molecule inhibitors of Heat Shock Protein 70 (HSP70) 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 College of Medicine and The University of Pennsylvania Raymond and Ruth Perelman School 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.

Selected Publications

1. Azzam GA, Wang X, Bell DA and Murphy ME.  CSF1 is a novel p53 target gene whose protein product functions in a feed-forward manner to suppress apoptosis and enhance p53-mediated growth arrest.  PLoS One, in press.

2. Budina-Kolomets A, Hontz RD, Pimkina J, Murphy ME. A conserved domain in exon 2 coding for the human and murine ARF tumor suppressor protein is required for autophagy induction. Autophagy 2013; Aug 7;9(10).  PMID: 23939042

3. Murphy ME. The HSP70 family and cancer. Carcinogenesis 2013; 34(6):1181-8. PMID: 23563090

4. Balaburski GM, Leu JI, Beeharry N, Hayik S, Andrake MD, Zhang G, Herlyn M, Villanueva J, Dunbrack RL Jr, Yen T, George DL, Murphy ME.  A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res 2013;11(3):219-29. PMID: 23303345

5. Leu JI, Pimkina J, Pandey P, Murphy ME, George DL.  HSP70 inhibition by the small-molecule 2-phenylethynesulfonamide impairs protein clearance pathways in tumor cells. Mol Cancer Res. 2011; 9:936-47. PMID: 21636681

6. 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;10:1352-5. PubMed PMID: 2156645

7. 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; 31:1201-13. PubMed PMID: 21245379; PubMed Central PMCID: PMC3067895.

8. Leu JI, Pimkina J, Frank A, Murphy ME, and George DL. A Small Molecule Inhibitor of Inducible Heat Shock Protein 70 (HSP70). Mol Cell 2009, 36:15-27. PMID: 19818706

9. Humbey O, Pimkina J, Zilfou JT, Jarnik M, Dominguez-Brauer C, Burgess DJ, Eischen CM, Murphy ME. The ARF tumor suppressor can promote the progression of some tumors. Cancer Res 2008; 68:9608-13. PubMed PMID: 19047137; PubMed Central PMCID:PMC2637809.

10. Dumont P, Leu JI, Della Pietra AC 3rd, George DL, Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 2003; 33:357-65. PubMed PMID: 12567188.