Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Christopher Counter

Christopher Counter, Ph.D.
Associate Professor of Pharmacology
Associate Professor of Radiation Oncology

Duke University Medical Center
C225 LSRC
Box 3813
Durham, NC 27710

Phone: 919-684-9890
E-mail: count004@mc.duke.edu

Research Interests

The Counter lab studies the molecular mechanisms underlying the evolution of normal cells into cancer. The lab is divided into three major areas studying key features of human cancers. Immortalization: We have shown that the ability of cancer cells to keep dividing, or become immortal, is a fundamental aspect of tumorigenesis, and is due to activation of the enzyme telomerase. Consequently, telomerase has now emerged as an attractive therapeutic target for the treatment of a wide spectrum of human cancers. Current efforts focus on the molecular biology of telomerase function and regulation in human cancer cells. Proliferation: The ability of tumor cells to proliferate inappropriately is a hallmark of cancer. One gene that plays a key role in this process is the oncogene Ras. We have shown that Ras exerts its oncogenic signals differently in mice and human cells, and as a result from these studies, have uncovered a pathway employed primarily in human cells during Ras oncogenesis. Current studies are aimed at understanding the molecular signaling of this oncogenic arm of Ras, and identifying other proteins that may similarly promote the unrestrained proliferation characteristic of cancer cells. In vivo tumor growth: While much can be learned about the processes of tumorigenesis in vitro, ultimately carcinogenic mutations empower cells with the ability to form tumors in vivo. In this regard, we are genetically dissecting the changes required to drive normal human cells to form tumors in vivo.

Publications

Hahn, W.C. * , Counter, C.M. * ( * both authors contributed equally to this work), Lundberg, A.S., Beijersbergen, R.L., Brooks, M.W. and Weinberg, R.A. (1999) Creation of Human Tumor Cells with Defined Genetic Elements. Nature , 400:464-468.

Rich, J.N., Guo, C., McLendon, R.E., Bigner, D.D., Wang, X-.F., and Counter, C.M. (2001) A Genetically Tractable Model of Human Glioma Formation. Cancer Res., 61:3556-3560.

Armbruster, B.N., Banik , S.S.R. , Guo, C., Smith, A.C., and Counter, C.M. (2001) N-Terminal Domains of the Human Telomerase Catalytic Subunit Required for Enzyme Activity In Vivo. Mol. Cell. Biol., 21: 7775-7786 .

Etheridge, K.E., Banik , S.S.R. , Armbruster, B.N., Zhu, Y., Terns, R.M., Terns, M.P. and Counter, C.M. (2002) The Nucleolar Localization Domain of the Catalytic Subunit of Human Telomerase. J. Biol. Chem., 277: 24764-24770.

Banik, S.S.R., Guo, C., Hamad, N.M., Shatkin-Margolis, S.N., Richardson, D.A., Smith, A.C., and Counter, C.M. (2002) Carboxyl-Terminal Domains of the Human Telomerase Catalytic Subunit Essential for Enzyme Function in vitro and in vivo. Mol. Cell. Biol., 22: 6234-6246.

Hamad, N.M., Elconin, J.E., Karnoub, A.E., Bai, W., Rich, J.N., Abraham, R.T., Der, C.J., and Counter, C.M. (2002) Distinct Requirements for Ras Oncogenesis in Human versus Mouse cells. Genes Dev., 16: 2045-2057.

Hamad , N.M. *, Banik , S.S.R. *, ( * both authors contributed equally to this work), and Counter, C.M. (2002) Mutational Analysis Defines a Minimum Level of Telomerase Activity Required for Tumourigenic Growth of Human Cells. Oncogene, 21:7121-7125.

Counter, C.M., Press, W., and Compton , C.C. (2003) Telomere Shortening in Cultured Autografts of Patients with Burns. Lancet, 361: 1345-1346.

Armbruster, B.N., Etheridge, K.T., Broccoli, D., and Counter, C.M. (2003) A Putative Telomere Recruiting Domain in the Catalytic Subunit of Human Telomerase. Mol. Cell. Biol., 23: 3237-3246.

McKee, J.A., Banik, S.S.R., Boyer, M.J., Hamad, N., Lawson, J.H., Niklason, L.E.,* and Counter, C.M..* (*shared corresponding authorship) (2003) Human Arteries Engineered in vitro. EMBO Reports, 4: 633-638 .

Armbruster, B.N., Linardic, C.M., Veldman, T., Bansal, N.P., Downie, D.L. and Counter, C.M. (2004) A Role for hPot1 in Telomerase-Mediated Telomere Replication. Mol. Cell. Biol., 24: 3552-3561.

Banik , S.S.R. , and Counter, C.M. (2004) Characterization of the interaction of PinX1 with telomerase. J. Biol. Chem., 279: 51745-51748 .

Veldman, T., Etheridge, K.T., and Counter, C.M. (2004) Loss of hPot1 function leads to telomere instability and a cut -like phenotype. Curr. Biol., 14: 2264-2270 .

Poh, M., Boyer, M., Solan, A., Mitchell, S., Pedrotty, D., Banik, S.S., McKee J.A., Counter, C.M. and Niklason L.E. (2005) Blood Vessels Engineered from Human Cells. Lancet, 365: 2122-2124.

Linardic, C.M., Downie, D.L., Bentley, R.C. and Counter, C.M. (2005) Genetic induction of human rhabdomyosarcoma. Cancer Res., 65: 4490-4495.

Lim K.-H., Baines, A.T., Fiordalisi, J.J., Shipitsin, M., Feig, L.A. , Cox, A.D., Der, C.J., and Counter, C.M. (2005) Activation of RalA is critical for Ras-induced tumorigenesis of human cells. Cancer Cell, 7: 533-545.

Kendall , S.D. *, Linardic, C.M.* ( * both authors contributed equally to this work), Adam, S.J., and Counter, C.M. (2005) A network of genetic events sufficient to convert normal human cells to a tumorigenic state. Cancer Res., 65: 9824-9828 .

Lim, K.-H., and Counter, C.M. (2005) Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance. Cancer Cell, 8: 381-392 .

Freibaum, B.D. and Counter, C.M. (2006) hSnm1B is a novel telomere-associated protein. J. Biol. Chem., 281:15033-15036.

Lim, K.-H., O’Hayer, K., Adam, S.J., Kendall, D., Cambell, P.M., Der, C.J.*, & Counter, C.M.* (*corresponding authors) (2006) Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cells. Curr. Biol., 16:2385-94.

Adam, S.J., Rund, L.A., Schook, L.B., & Counter, C.M. (2007) Genetic induction of tumorigenesis in swine. Oncogene, 26:1038-45.

Linardic, C.M., Naini, S., Qualman, S., & Counter, C.M. (2007) The PAX3-FRHD fusion gene of Rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence. Cancer Res., 67: 6691-6699.

Ancrile, B., Lim, K.-H., & Counter, C.M. (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev., 21: 1714-1719.

Etheridge KT, Compton SA, Barrientos KS, Ozgur S, Griffith JD & Counter CM (2008). Tethering telomeric double- and single-stranded DNA binding proteins inhibits telomere elongation. J Biol Chem, 283: 6988-96.

Lim K-H*, Ancrile BB*, Kashatus D* (*these authors contributed equally) & Counter CM (2008) eNOS mediates tumour maintenance. Nature 452: 646-50.

Barrientos KS*, Kendellen MF* (*these authors contributed equally), Freibaum, BD, Armbruster BN, Etheridge KT & Counter CM (2008) Distinct functions of POT1. Mol Cell Biol, in press.

Freibaum BD & Counter CM (2008) The protein hSnm1B is stabilized when bound to the telomere-binding protein TRF2. J Biol Chem, in press.

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