I have long been interested in how cells acquire unique identities during development and maintain their identities throughout adulthood. The Wnt/beta-catenin signaling pathway regulates diverse cell fates and renews stem cells, and its altered activity causes human disease. My research lab has investigated how Wnt/beta-catenin signal transduction is regulated by Naked cuticle (Nkd) proteins in flies, mice, and human cancer. Our studies revealed that Nkd acts via a feedback loop to target the Wnt signal transducer Dishevelled in multiple subcellular compartments. We also showed that mice lacking Nkd activity are viable with a phenotype that resembles the loss of another Wnt antagonist, Axin2. Humans with altered Nkd activity have yet to be recognized, but our studies in flies and mice suggest that Nkd proteins fine-tune signaling in every tissue where Wnt signals govern cell behavior.
At present I serve as Associate Dean of Undergraduate Medical Education, responsible for the first two years of medical school, the “basic science” years. In this capacity I plan to help ensure that these crucial years of training are of outstanding quality and utmost relevance to our diverse student body.
RESEARCH INTERESTS
Pattern Formation
Genetic Regulatory Systems
Gene Expression
Developmental Biology
Cancer
RECENT PUBLICATIONS
Chan, C.-C., Zhang, S., Rousset, R., Wharton, K.A. Jr., "Drosophila Naked cuticle (Nkd) engages the nuclear import adaptor Importin alpha3 to antagonize Wnt/beta-catenin signaling." Dev. Biol., 318:17-28, 2008
Chan, C.-C., Zhang, S., Cagatay, T, Wharton, K. A. Jr., "Cell-autonomous, myristyl-independent activity of the Drosophila Wnt/Wingless antagonist Naked cuticle (Nkd)" Dev. Biol., 311:538-53, 2007
Zhang, S., Cagatay, T., Amanai, M., Zhang, M., Kline, J., Castrillon, D. H., Ashfaq, R., Oz, O. K., Wharton, K. A. Jr., "Viable mice with compound mutations in the Wnt/Dvl-pathway antagonists nkd1 and nkd2" Mol. Cell. Biol., 27:4454-4464, 2007
Waldrop, S., Chan, C. C., Cagatay, T., Zhang, S., Rousset, R., Mack, J., Zeng, W., Fish, M., Zhang, M., Amanai, M., Wharton, K. A., Jr., "An unconventional nuclear localization motif is crucial for function of the Drosophila Wnt/Wingless antagonist Naked cuticle" Genetics, 174:331-348, 2006
Zhang, L., Jia, J., Wang, B., Amanai, K., Wharton, K. A. Jr., Jiang J., "Regulation of Wingless signaling by the CKI family in Drosophila limb development." Dev. Biol., 299:221-237, 2006
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