Dianqing (Dan) Wu PhD

Professor of Pharmacology

Research Interests

Wnt; signal transduction; G protein, Chemotaxis;Cell migration; Cancer biology and therapeutics; Stem cell biology; Chemoattractant signaling; Inflammation

Current Projects

1) Wnt signaling mechanisms and functions
2) Regulation of neutrophil migration
3) Atherosclerosis
4) Wnt signaling in bone development and diseases
5) Wnt signaling and stem cell biology

Research Summary

Dr. Wu’s lab is interested in the mechanisms and functions of chemoattractant and Wnt-activated signaling. Chemoattractants, including chemokines, play an important role in host defense. However, their unchecked activities contribute to may inflammation-related diseases, including atherosclerosis, arthritis, tumorigenesis, and various allergies. The Wnt family of secretory glycoproteins participates in a wide variety of developmental events including, control of cell growth, generation of cell polarity, and specification of cell fate. Wnt pathways have been also closely linked to tumorigenesis, glucose metabolism, and bone formation. We are using a combination of molecular and cell biological, biochemical, chemical biological, transgenic, functional genomic, and proteomic approaches to discover novel signaling mechanisms and functions for these signaling proteins.

Extensive Research Description

Our long-term goal is to understand the molecular basis and function of signal transduction pathways, with the emphasis on those initiated by seven-transmembrane receptors. These receptors can be divided into two groups: one couples to heterotrimeric GTP-binding proteins; and the other binds to ligands including hedgehog proteins and Wnt proteins. Currently, we are focusing on chemoattractant and Wnt-activated signaling. Chemoattractants, including the superfamily of chemotactic cytokines, chemokines, play an important role in host defense by attracting and activating leukocytes at sites of injury and infection. However, their unchecked activities contribute to may inflammation-related diseases, including atherosclerosis, arthritis, tumorigenesis, and various allergies. Work in my lab has made significant contributions to the understanding of signaling mechanisms and functions of a number of chemoattractant-activated pathways. These include pathways linked by PLC ß, PI3K?, PIXa/Pak/Cdc42, PTEN, P-Rex1, and Myo1f. We are continuing to use a combination of molecular and cell biological, biochemical, transgenic, functional genomic, and proteomic approaches to characterize novel chemoattractant signaling mechanisms and study their functions in cell migration and inflammation-related paradigms. The Wnt family of secretory glycoproteins participates in a wide variety of developmental events including, control of cell growth, generation of cell polarity, and specification of cell fate. Wnt pathways have been also closely linked to tumorigenesis and bone formation. Most notable contributions from my is the discovery of the interaction between Wnt coreceptor LRP-5 and Axin, which provides the first connection from a Wnt receptor to a intracellular signaling component and the characterization of the role of Dkk2 in regulation of osteogenic differentiation. We are continuing to work on the elucidation of fundamental mechanisms of Wnt signaling and characterization of their role in pathophysiological processes, including osteoporosis, metabolic syndrome, diabetes, and tumorigenesis, using computation-based virtual screening and chemical genomic approaches, in addition to the aforementioned ones.


Selected Publications

  • Zhang, Y., Tang, W., Zhang H., Niu, X., X, Y., Zhang, J., Gao, K., Pan, W., Boggon, T.J., Toomre, D., Min, W., Wu, D. (2013) A network of interactions enables CCM3 and STK24 to coordinate UNC13D-driven vesicle exocytosis in neutrophils. Developmental Cell, 2013. 27: 215-26.
  • Kim, I., Pan, W., Jones, S.A., Zhang, Y., Zhuang, X., and Wu, D. (2013). Clathrin and AP2 are required for PtdIns(4,5)P2-mediated formation of LRP6 signalosomes. J Cell Biol 200, 419-428
  • Gan, X., Wang, J., Wang, C., Sommer, E., Kozasa, T., Srinivasula, S., Alessi, D., Offermanns, S., Simon, M.I., and Wu, D. (2012). PRR5L degradation promotes mTORC2-mediated PKC-d phosphorylation and cell migration downstream of Ga12. Nat Cell Biol. 10.1038/ncb2507
  • Tang, W., Zhang, Y., Xu, W., Harden, T.K., Sondek, J., Sun, L., Li, L., and Wu, D. (2011). A PLCb/PI3Kg-GSK3 Signaling Pathway Regulates Cofilin Phosphatase Slingshot2 and Neutrophil Polarization and Chemotaxis. Developmental Cell 21, 1038-1050.
  • Xu, W., Wang, P., Petri, B., Zhang, Y., Tang, W., Sun, L., Kress, H., Mann, T., Shi, Y., Kubes, P., and Wu, D. (2010). Integrin-induced PIP5K1C kinase polarization regulates neutrophil polarization, directionality, and in vivo infiltration. Immunity 33, 340-350.
  • Pan, W., Choi, S.C., Wang, H., Qin, Y., Volpicelli-Daley, L., Swan, L., Lucast, L., Khoo, C., Zhang, X., Li, L., et al. (2008). Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science 321, 1350-1353.
  • Wang, Z., Liu, B., Wang, P., Dong, X., Fernandez-Hernando, C., Li, Z., Hla, T., Claffey, K., Smith, J.D., and Wu, D. (2007). Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest 118, 195-204
  • Li, Z., X. Dong, Z. Wang, W. Liu, N. Deng, Y. Ding, L. Tang, T. Hla, R. Zeng, L. Li and D. Wu., (2005) Regulation of PTEN by small GTPases. Nat. Cell Biol., 7399-404. (News & Views, Nat Cell Biol 7334 Editors’ Choice, Science 308327)
  • Li, X., Liu, P., Liu, W., Zhang, J., Boskey, A., Harris, E. S., Rowe, D., Ke, HuaZhu, and Wu, D. (2005). Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet, 37, 945-952
  • Li, Z., Hannigan, H, Mo, Z., Liu. B, Lu, W., Wu, Y., Smrcka, A.V., Wu, G., Liu, M., Huang, C-H., and Wu, D. (2003) Directional Sensing Requires G??-Mediated PAK1 and PIX?-Dependent Activation of Cdc42. Cell 114,215-227. [Mini-review, Cell 114 153-156]

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