UAMS Biochemistry Faculty - Timothy Chambers, Ph.D.

Our laboratory is interested in basic aspects of cancer chemotherapy, especially the mechanisms that link drug-induced damage to destruction or protective cellular responses. We have two main projects. One is to study the role of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated group of protein kinases, in drug-induced apoptosis and cell cycle regulation. The other is to investigate the role of phosphorylation of Bcl-2 proteins in apoptosis induced by antimitotic drugs. These projects are funded through two RO1s from the National Cancer Institute.

Brantley-Finley, C., Lyle, C.S., Du, L., Goodwin, M., Hall, T., Szwedo, D., Kaushal, G.P., and Chambers, T.C. (2003) The JNK, ERK and p53 Pathways Play Distinct Roles in Apoptosis Mediated by the Antitumor Agents Vinblastine, Doxorubicin, and Etoposide. Biochemical Pharmacology. 66, 459-469. Abstract

Jia, J., Alaoui-El-Azher, M., Chow, M., Baker, H., Chambers, T.C., and Jin, S. (2003) JNK Mediated Signaling is Essential for Pseudomonas aeruginosa ExoS Induced Apoptosis. Infec. Immun. 71, 3361-3370. Abstract

Du, L., Lyle, C.S., Hall-Obey, T., Gaarde, W.A., Muir, J.A., Bennett, B.L., and Chambers, T.C. (2004) Inhibition of Cell Proliferation and Cell Cycle Progression by Specific Inhibition of Basal JNK Activity. J. Biol. Chem. 279, 11957-11966. Abstract

Zharov, V.P., Galitovsky, V., Chowdhury, P., and Chambers, T.C. (2004) Photothermal Evaluation of the Influence of Nicotine, Antitumor Drugs, and Radiation on Cellular Absorbing Structures. Proc. SPIE 5320, 196-207.

Bene, A., Kurten, R.C., and Chambers, T.C. (2004) Subcellular Localization as a Limiting Factor for Utilization of Decoy Oligonucleotides. Nucleic Acids Res. 32, e142. Abstract

Kurten, R.C., Chowdhury, P., Sanders, R.C., Pittman, L., Sessions, L., Chambers, T.C., Lyle, C.S., Schackenberg, B.J., and Jones, S.M. (2005) Coordinating Epidermal Growth Factor Induced Motility Promotes Efficient Wound Closure. Am. J. Physiol. 288, C109-121. Abstract

Du, L., Lyle, C.S., Chambers, T.C. (2005) Characterization of Vinblastine-Induced Bcl-xl/Bcl-2 Phosphorylation. Evidence For a Novel Protein Kinase and a Phosphorylation- Dephosphorylation Cycle Associated with Apoptosis Induction. Oncogene 24, 107-117. Abstract

Obey, T. B., Lyle, C.S., and Chambers, T.C. (2005) Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine. Biochem. Biophys. Res. Comm. 335, 1179-1184. Abstract

Upreti, M., Lyle, C.S., Skaug, B., Du, L., and Chambers, T.C. (2006) Vinblastine-induced apoptosis is mediated by discrete alterations in the subcellular distribution, oligomeric structure, and activation status of specific Bcl-2 family members. J. Biol. Chem. 281, 15941-15950.

Zharov, V. Galitovsky, V., Lyle, C.S., and Chambers, T.C. (2006) Rapid photothermal monitoring of individual cell response of antitumor drug. J. Biomed. Optics (in press)

Unal, R., Ahmed, B.A., Jeffus, B.C., Harney, J.T., Lyle, C.S., Wu, Y-K., Chambers, T.C., Reece, E.A., and Kilic, F. (2006) At diabetes-like concentration, glucose down-regulates the placental serotonin transport system in a cell-cycle dependent manner. J. Neurochem. (in press)

Duan, L., Sterba, K., Kolomeichuk, S., Kim, H., Brown, P.H., and Chambers, T.C. (2006) Inducible overexpression of c-Jun in MCF7 cells causes resistance to vinblastine via inhibition of drug-induced apoptosis and senescence at a step subsequent to mitotic arrest. Biochem. Pharmacol. (in press)