Joseph G. Cory
Professor of Biochemistry & Molecular Biology
B.S., University of Tampa, 1958
Ph.D., Florida State University, 1963

Biochemistry, Molecular Biology, and Pharmacology of Tumor Cells

• regulation of cell proliferation
• factors regulating cell cycle/apoptosis
• molecular bases of drug resistance
• ribonucleotide reductase as a target for chemotherapy
• enzymes of nucleotide metabolism
• mode of action of new antitumor agents

Selected Publications

Contact Information

Faculty Page

Tumor Cells

Tumor cells are characterized by an inherent lack of normal control mechanisms for cell proliferation. There are many aspects involved in understanding the metabolic regulatory functions in cell cycle control and when interfered with leads to apoptosis. Processes of nucleotide synthesis and interconversions are critical for DNA replication and hence, cell division. One aspect that we have focused on is the study of the enzyme ribonucleotide reductase (RR), that catalyzes the rate-limiting step in the de novo synthesis of 2’-deoxyribonucleoside 5’-triphosphates required for DNA synthesis. The studies of the enzymolozy, biochemistry and cell biology of this enzyme have provided the bases for the development of chemotherapy directed at this target. Drug-resistant cells selected for resistance to drugs targeted for each subunit of RR have provided useful cellular models in which to study perturbations in cell cycle control. These drug-resistant tumor cell lines also provide a system in which to study factors that control the apoptotic responses in tumor cells. Our overall goal is to provide basic biochemistry, biological and pharmacological data that can be translated into useful treatments of human cancer. (top)

Selected Publications

Lin, Z.P., Belcourt, M.F., Carbone, R., Eaton, J.S. Penketh, P.G., Shadel, G.S., Cory, J.G. and Sartorelli, A.C. “Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress” Biochem. Pharmacol. (in press) 2007.

Cory, A.H. and Cory, J.G. “Critical Roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: Asparaginase treatment in childhood acute lymphoblastic leukemia” In Vivo. 20: 587-590 (2006)

Dinka-Kostova, A.T., Cory, A.H., Bozak, R.E., Hicks, R.J. and Cory, J.G. “Bis (2 hyrdoxybenzylidene) acetone, potent inducer of the phase 2 response, causes apoptosis in mouse leukemia cells through a p53-independent, caspase-meditated pathway” Cancer Letters. 21: 1-9 (2006).

Cory, A.H., Chen, J. and Cory, J.G. “Effects of PRIMA-1 on wild type L1210 cells expressing mutant p53 and drug-resistant L1210 cells lacking the expression of p53: necrosis vs apoptosis” Anticancer Res. 26: 1289-1296 (2006).

Cory, A.H., Somerville, L. and Cory, J.G. “Blockage of cyclin cdk’s PKC and phosphoinositol 3-kinase pathways leads to augmentation of apoptosis in drug-resistant leukemia cells: evidence for interactive effects of flavopiridol, LY 294002, wortmannin and UCN-01” Anticancer Res. 25: 101-106 (2005).

Cory, A.H. and Cory, J.G. “Induction of apoptosis in p53-deficient L1210 cells by an I kappa B alpha inhibitor (Bay 11-7085) via a NF kappa B-independent process” Advan Enzyme Regul. 45: 85-93 (2005).

Cory, A.H. and Cory, J.G. “Phenolic compounds, sodium salicylate and related compounds, as inhibitors of tumor cell growth and inducers of apoptosis in mouse leukemia L1210 cells” In Vivo. 19: 31-36 (2005).

Lin, Z.P., Belcourt, M.F., Cory, J.G. and Sartorelli, A.C. “Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53 (-1-) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors” J. Biol. Chem. 279: 27030-27038 (2004).

Cory, A.H. and Cory, J.G. “Gemcitabine-induced Apoptosis in a Drug-resistant Mouse Leukemia L1210 Cell Line that does not Express p53” Adv. Enzyme Regul. 44: 11-25 (2004).

Cory, A.H., Edwards, C.C., Hall, J.G. and Cory, J.G. “Inhibitors of Diverse Metabolic Steps Cause Increased Apoptosis in Deoxyadenosine-resistant Mouse Leukemia L1210 Cells that Lack p53: Convergence at Caspase-3 Activation” Adv. Enzyme Regul. 43: 29-45 (2003).

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Contact Information

Professor of Biochemistry & Molecular Biology

Brody 5S-22

The Brody School of Medicine at East Carolina University

Greenville, NC 27834

phone: 252.744.2675

email:  coryjo@ecu.edu

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