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. Dr. 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, Dr. 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.
Chatwichien J, Basu S, Murphy ME, Hamann MT, Winkler JD: Design, Synthesis and Biological Evaluation of β-Carboline Dimers Based on the Structure of Neokauluamine. Tetrahedron Lett. 2015.
Kung CP, Khaku S, Jennis M, Zhou Y and Murphy ME. : Identification of TRIML2, a Novel p53 Target, that Enhances p53-SUMOylation and Regulates the Transactivation of Pro-apoptotic Genes. Mol Cancer Res 2015.
Bailey CK, Budina-Kolomets A, Murphy ME, Nefedova Y: Efficacy of the HSP70 inhibitor PET-16 in multiple myeloma. Cancer Biol Therapy 2015.
Budina-Kolomets A, Balaburski GM, Bondar A, Beeharry N, Yen T, and Murphy ME: Comparison of the activity of three different HSP70 inhibitors on apoptosis, cell cycle arrest, autophagy and HSP90 function. Cancer Biol There 2014.
Malecka KA, Fera D, Schultz DC, Hodawadekar S, Reichman M, Donover PS, Murphy ME, Marmorstein R: Identification and Characterization of Small Molecule Human Papillomavirus E6 Inhibitors. ACS Chem Biol 2014.
Zhang P, Leu JIJ, Murphy ME, George DL and Marmorstein R: Crystal Structure of the Stress-Inducible Human Heat Shock Protein 70 Substrate-Binding Domain in Complex with Peptide Substrate. PLoS One 2014.
Leu JIJ, Zhang P, Murphy ME, Marmorstein R and George DL. : Structural Basis for Inhibition of HSP70 and DnaK Chaperones by Small-Molecule-Targeting of a C Terminal Allosteric Pocket. ACS Chem Biol 2014.
Balaburski GM, Leu JIJ, Beeharry N, Hayik S, Andrake MD, Zhang G, Herlyn M, Villanueva J, Dunbrack Jr RL, Yen T, George DL and Murphy ME: A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res 2013.
Budina-Kolomets A, Hontz RD, Pimkina J and Murphy ME: A conserved domain in exon 2 of the human and murine ARF tumor suppressor protein is required for autophagy induction. Autophagy 2013.
Azzam G, Bell D, Wang X 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 2013.
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Last updated: 08/20/2015
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