Virshup, David M.

Research Interests:

David Virshup, MD, is the inaugural Director of the Program in Cancer and Stem Cell Biology at the newly established Duke-NUS Graduate Medical School in Singapore. Until July, 2007, he was an investigator at the Huntsman Cancer Institute, and the first Willard Snow Hansen Presidential Professor of Cancer Research at the University of Utah. While spending the majority of his time on laboratory-based research, he is also a practicing pediatric hematologist/oncologist. His laboratory studies protein phosphorylation, a key signaling mechanism, and its effects on circadian rhythms and cell proliferation. Virshup received his medical degree from Johns Hopkins University School of Medicine in 1981. He completed his clinical training in Pediatrics and Pediatric Hematology/Oncology at Johns Hopkins. His research training was in the departments of Pediatrics, Cell Biology and Anatomy, and Molecular Biology and Genetics at Johns Hopkins.

Wnt signaling is a highly conserved pathway important in stem cell maintenance, cell proliferation, cancer and development. The Virshup laboratory studies the Wnt signaling pathways with a emphasis on the protein kinases and phosphatases that are regulated by Wnt, and that control the fate of cells.

Selected Publications:

Tsai, I.C., Woolf, M., Neklason, D.W., Branford, W.W., Yost, H.J., Burt, R.W., and Virshup, D.M. 2007. Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism. International journal of cancer 120: 1005.

Tsai, I., Amack, J., Gao, Z., Band, V., Yost, H., and Virshup, D. 2007. A Wnt-CKIvarepsilon-Rap1 pathway regulates gastrulation by modulating SIPA1L1, a Rap GTPase activating protein. Developmental cell 12: 335.

Luo, W., Peterson, A., Garcia, B., Coombs, G., Kofahl, B., Heinrich, R., Shabanowitz, J., Hunt, D., Yost, H., and Virshup, D. 2007. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. The EMBO journal 26: 1511.

Swiatek, W., Kang, H., Garcia, B.A., Shabanowitz, J., Coombs, G.S., Hunt, D.F., and Virshup, D.M. 2006. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. J Biol Chem 281: 12233.

Margolis, S.S., Perry, J.A., Forester, C.M., Nutt, L.K., Guo, Y., Jardim, M.J., Thomenius, M.J., Freel, C.D., Darbandi, R., Ahn, J.H., Arroyo, J.D., Wang, X.F., Shenolikar, S., Nairn, A.C., Dunphy, W.G., Hahn, W.C., Virshup, D.M., and Kornbluth, S. 2006. Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell 127: 759.

Eide, E., Woolf, M., Kang, H., Woolf, P., Camacho, F., Vielhaber, E., Giovanni, A., and Virshup, D. 2005. Control of mammalian circadian rhythm by CKIe-regulated proteasome-mediated PER2 degradation. Molecular and Cellular Biology 25: 2795.

Swiatek, W., Tsai, I.C., Klimowski, L., Pepler, A., Barnette, J., Yost, H.J., and Virshup, D.M. 2004. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem 279: 13011.

Li, X., Scuderi, A., Letsou, A., and Virshup, D.M. 2002. B56-Associated Protein Phosphatase 2A Is Required For Survival and Protects from Apoptosis in Drosophila melanogaster. Mol Cell Biol 22: 3674.

Li, X., Yost, H.J., Virshup, D.M., and Seeling, J.M. 2001. Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO Journal 20: 4122.

Meng QJ, Logunova L, Maywood ES, Gallego M, Lebiecki J, Brown TM, Sládek M, Semikhodskii AS, Glossop NR, Piggins HD, Chesham JE, Bechtold DA, Yoo SH, Takahashi JS, Virshup DM, Boot-Handford RP, Hastings MH, Loudon AS. (2008) Setting clock speed in mammals: the CK1ε^tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins. Neuron 58:78-88.

Gary S Coombs, Jia Yu, Claire A Canning, Charles A Veltri, Tracy M Covey, Jit K Cheong, Velani Utomo, Nikhil Banerjee, Zong Hong Zhang, Raquel C Jadulco, Gisela P Concepcion, Tim S Bugni, Mary Kay Harper, Ivana Mihalek, C. Michael Jones, Chris M Ireland, and David M Virshup. (2010) WLS/GPR177-dependent secretion of WNT3A requires serine 209 acylation and vacuolar acidification. Journal of Cell Science, 123(19): 3357-67

Jit Kong Cheong, Nguyen Thanh Hung, Hannah Wang, Patrick Tan, P. Mathijs Voorhoeve, Sang Hyun Lee and David M Virshup. (2011) IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ε and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene, in press

Gary S. Coombs, Allison A. Schmitt, Claire A. Canning, Anshula Alok, Ivan Cherh Chiet Low, Nikhil Banerjee, Simran Kaur, Velani Utomo, C. Michael Jones, Shazib Pervaiz, Eric J. Toone, and David M. Virshup. (2011) Modulation of Wnt/β-catenin signaling and proliferation by a ferrous iron chelator with therapeutic efficacy in genetically engineered mouse models of cancer. Oncogene, in press.