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Timothy C. Chambers, Ph.D.

Professor and Vice Chair

Ph.D., University of Portsmouth, UK

 

 

 

Cytotoxic signaling mechanisms of anticancer drugs

Our laboratory is interested in basic aspects of cancer chemotherapy, especially the mechanisms that link drug-induced damage to destructive or protective cellular responses.  Our focus has been on understanding the role of Bcl-2 proteins in the mechanism of action of microtubule inhibitors and other anti-mitotic drugs. 

Selected Publications

Kolomeichuk, S.N., Bene, A., Upreti, M., Dennis, R.A., Lyle, C.S., Rajasekaran, M., and Chambers, T.C.  (2008) Induction of apoptosis by vinblastine via c-Jun auto-amplification and p53-independent regulation of p21WAF1/CIP1.  Mol. Pharmacol. 73, 128-136.

 

Kolomeichuk, S.N., Terrano, D., Lyle, C.S., Sabapathy, K., and Chambers, T.C. (2008) Distinct signaling pathways of microtubule inhibitors - vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively.   FEBS Journal.  275, 1889-1899. 

 

Upreti, M., Chu, R., Galitovskaya, E.N., Smart, S., and Chambers, T.C. (2008) Critical role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine.  Mol. Cancer Therap.  7, 2233-2240. 

 

Upreti, M., Galitovskaya, E.N., Chu, R., Tackett, A.J., Terrano, D.T., Granell, S., and Chambers, T.C. (2008) Identification of the major phosphorylation site in Bcl-xL induced by microtubule inhibitors and analysis of its functional significance.  J. Biol. Chem.  283, 35517-35525.

 

Bene, A., and Chambers, T.C. (2009) p21 functions in a post-mitotic block checkpoint in the apoptotic response to vinblastine.  Biochem. Biophys. Res. Commun. 380, 211-217.

 

Chu, R., Upreti, M., Ding, W-X., Yin, X-M, and Chambers, T.C. (2009) Regulation of Bax by c-Jun NH2-terminal kinase and Bcl-xL in vinblastine-induced apoptosis.  Biochem. Pharmacol.  78, 241-248.

 

Bateman, T.D., Joshi, A.L., Moon, K., Galitovskaya, E.N., Upreti, M., Chambers, T.C., and McIntosh, M.C.  (2009) Synthesis and anticancer activity of sclerophytin-inspired hydroisobenzofurans.  Bioorg. Med. Chem. Lett. 19, 6898-6901.

 

Terrano, D.T., Upreti, M., and Chambers, T.C.  (2010) Cyclin-dependent kinase-1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis.  Mol. Cell. Biol. 30, 640-656.

                   

 

Pubmed link for additional publications

   
E-mail: ChambersTimothyC@uams.edu
Office (501) 686-5755  Biomedical Research Center B405F
Lab: (501) 686-5756  Biomedical Research Center B403/404
FAX: (501) 686-8169

  

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Department of Biochemistry and Molecular Biology
University of Arkansas for Medical Sciences
4301 W. Markham St., Slot 516
Little Rock, AR 72205