My research activities focus on developing target molecular therapies for advanced childhood cancers. With research training in genetically-engineered mouse models in the laboratory of 2007 Nobel laureate Mario Capecchi, I have developed and study mouse models of the childhood muscle cancer rhabdomyosarcoma and the brain tumor medulloblastoma. Using conditional genetics to temporally and spatially restrict Pax3:Fkhr oncogene expression to subsets of embryonic and postnatal muscle cell precursors, it is hoped that rhabdomyosarcomas can be understood in terms of their cell of origin while at the same time unraveling the step-by-step process of rhabdomyosarcoma formation, angiogenesis, and metastasis.

In addition to my research, I am also Director of the GCCRI Small Animal Imaging Facility, which provides service and conducts research into anatomical and molecular imaging methods for mouse models of human disease and muscle stem cell biology.

Keywords:

rhabdomyosarcoma, medulloblastoma, genetically engineered mice, satellite cell, muscle stem cell, receptor tyrosine kinase, preclinical therapeutics, small animal imaging

Selected Publications:

Eri Taniguchi, Koichi Nishijo, Amanda T. McCleish, Joel E. Michalek, Robin D. Legallo, Stephen J. Qualman, Hanna E. Abboud, Brian P. Rubin, Charles Keller. PDGFR-A is a Therapeutic Target in Alveolar Rhabdomyosarcoma. Oncogene, 2008 (in press).

Andrew S. Brack, Michael J. Conboy, Mark Lee, Sudeep Roy, Calvin J. Kuo, Charles Keller, Thomas A. Rando. Elevated Wnt signaling during aging alters the fate of myogenic stem cells leading to increased fibrosis and impaired muscle regeneration. Science, 2007 August, 317:807-810.

Ali N. Bahadur, Isabel Q. Wu, David M. Weinstein, M. Duff Davis, David A. Lewis, Peter Kochunov, Charles Keller. Stealth, Safe Multi-modality Chamber for Co-registered Anatomical and Molecular Small Animal Imaging, Lab Animal, 2007 September, 36(8):29-35.

Mary Blandford, Frederic G. Barr, James C. Lynch, R. Lor Randall, Stephen J. Qualman, Charles Keller. Rhabdomyosarcomas Utilize Developmental Myogenic Growth Factors for Disease Advantage, Pediatric Blood and Cancer, 2006 March, 46(3):329-38.

John T. Johnson, Mark S. Hansen, Isabel Wu, Lindsey J. Healy, Christopher R. Johnson, Greg M. Jones, Mario R. Capecchi, Charles Keller. Virtual Histology of Transgenic Mouse Embryos for High-Throughput Phenotyping, PLoS Genetics, 2006, 2(4)e61.

Gordon L. Kindlmann, David M. Weinstein, Greg M. Jones, Christopher R. Johnson, Mario R. Capecchi, Charles Keller. Practical Vessel Imaging by Computed Tomography in Live Transgenic Mouse Models for Human Tumors, Molecular Imaging, 2005 Oct; 4(4):417-24.

Charles Keller, Mario R. Capecchi. New Genetic Tactics to Model Alveolar Rhabdomyosarcoma in the Mouse, Cancer Research, 2005, 65:7530.

Charles Keller, Ben Arenkiel, Nabeel El-Bardeesy, Cheryl Coffin, Ronald DePinho, Mario Capecchi. Alveolar Rhabdomyosarcomas in Conditional Pax3:Fkhr Mice: Cooperativity of Ink4a/ARF and Trp53 Loss of Function, Genes & Development, 2001 November, 18(21):2614-26.

Charles Keller, Mark S. Hansen, Cheryl Coffin, Mario Capecchi. Pax3:Fkhr interferes with Embryonic Pax3 and Pax7 Function: Implications for Alveolar Rhabdomyosarcoma Cell of Origin, Genes & Development, November 2004, 18(21):2608-13.