Our research objectives are to determine 1) the role of p53 in radiation sensitivity and cell cycle delay, 2) the mechanisms by which interferon beta enhances the radiation sensitivity of human tumor cells and 3) the biochemical and functional properties of G2/M checkpoint proteins.

The relationships between p53 and radiation sensitivity are being investigated with mouse cell lines transfected with different forms of p53 mutations. The results will determine the phenotypic and functional changes of p53 and their involvement in the radiation sensitivity of mammalian cells. The goal of the interferon study is to investigate whether its effect on radiation sensitivity is mediated through the Ku 70/80 and DNA-dependent protein kinase (DNA-PK) activity. Ku 70/80 and DNA-PK are known to be involved in the repair of radiation-induced DNA double-strand breaks. A better understanding of the interaction between interferon beta and radiation would improve the efficacy of cancer therapy with combined treatments of radiation and drugs.

We are also studying the function of a yeast G2/M checkpoint gene, rad9, in mammalian cells. Mutation of rad9 in yeast abrogates the function of G2/M arrest and makes the cells very sensitive to ionizing radiation. We have identified a rad9 equivalent gene from the human lung tumor A549 cells. The expression of this gene as a function of the cell cycle is being investigated after various radiation conditions. We plan to explore the role of rad9 in G2/M arrest and radiation sensitivity of human tumor cells.

Recent Publications

Brandt PD, Helt CE, Keng PC, Bambara RA. 2006. The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation. Biochem Biophys Res Commun. Jun 21;

Mao W, Iwai C, Keng PC, Vulapalli R, Liang CS. 2006. Norepinephrine-induced oxidative stress causes PC-12 cell apoptosis by both endoplasmic reticulum stress and mitochondrial intrinsic pathway: inhibition of phosphatidylinositol 3-kinase survival pathway. Am J Physiol Cell Physiol. May;290(5):C1373-1384.

Lee YJ, Sheu TJ, Keng PC. 2005. Enhancement of radiosensitivity in H1299 cancer cells by actin-associated protein cofilin. Biochem Biophys Res Commun. Sep 23;335(2):286-91.

Helt CE, Wang W, Keng PC, Bambara RA. 2005. Evidence that DNA damage detection machinery participates in DNA repair. Cell Cycle. Apr;4(4):529-532

McCollum G, Keng PC, States JC, McCabe MJ Jr. 2005. Arsenite delays progression through each cell cycle phase and induces apoptosis following G2/M arrest in U937 myeloid leukemia cells. J Pharmacol Exp Ther. May;313(2):877-87.

Mazzatti DJ, Lee YJ, Helt CE, O’Reilly MA, Keng PC. 2005. p53 modulates radiation sensitivity independent of p21 transcriptional activation. Am J Clin Oncol. Feb;28(1):43-50

Helt CE, Cliby WA, Keng PC, Bambara RA, O’Reilly MA. 2005. Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage. J Biol Chem. Jan 14;280(2):1186-1192

Abeysinghe HR, Pollock SJ, Guckert NL, Veyberman Y, Keng P, Halterman M, Federoff HJ, Rosenblatt JP, and Wang N. 2004. The role of the THY1 gene in human ovarian cancer suppression based on transfection studies. Cancer Genet Cytogenet. Feb;149(1):1-10.

Chen MF, Wu CT, Chen YJ, Keng PC, Chen WC. 2004. Cell Killing and Radiosensitization by Caffeic Acid Phenethyl Ester (CAPE) in Lung Cancer Cells. J Radiat Res (Tokyo). Jun;45(2):253-260.

Mao W, Qin F, Iwai C, Vulapalli R, Keng PC, and Liang CS. 2004. Extracellular norepinephrine reduces neuronal uptake of norepinephrine by oxidative stress in PC12 cells. Am J Physiol Heart Circ Physiol. Jul;287(1):H29-39.

Roper JM, Mazzatti DJ, Watkins RH, Maniscalco WM, Keng PC, and O’Reilly MA. 2004. In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. Am J Physiol Lung Cell Mol Physiol. May;286(5):L1045-1054.

Helt CE, Staversky RJ, Lee YJ, Bambara RA, Keng PC,and O’Reilly MA. 2003. The CDK and PCNA domains on p21 Cip1 both function to inhibit G1/S progression during hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L506-13

Roper JM, Staversky RJ, Finkelstein JN, Keng PC, and O’Reilly MA. 2003. Identification and isolation of mouse type II cells on the basis of intrinsic expression of enhanced green fluorescent protein. Am J Physiol Lung Cell Mol Physiol. Sep;285(3):L691-700.

Chen Y, Pandya K, Keng PC, Johnstone D, Li J, Lee YJ, Smudzin T, and Okunieff P. 2003. Phase I/II Clinical Study of Pulsed Paclitaxel Radiosensitization for Thoracic Malignancy: A Therapeutic Approach on the Basis of Preclinical Research of Human Cancer Cell Lines. Clin Cancer Res. Mar;9(3):969-975.

O’Reilly MA, Staversky RJ, Finkelstein JN, and Keng, PC. 2003. Activation of the G2 cell cycle checkpoint enhances survival of epithelial cells exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol. Feb;284(2):L368-375.

Rancourt RC, Hayes DD, Chess PR, Keng PC, O'Reilly MA 2002. Growth arrest in G1 protects against oxygen-induced DNA damage and cell death. J Cell Physiol. Oct;193(1):26-36.