Regulation of primary cilia and their role in development and human disease.
We study the role of primary cilia, small antennae-like organelles that project from the surface of cells, in mediating cell signaling. While the function of these structures was a long-standing mystery in cell biology, work over the past decade has established an essential role for cilia in mediating signaling through the Hedgehog pathway, a critical developmental signaling pathway. In addition, a number of human genetic disorders are linked to disruptions in cilia structure or function. In spite of the emerging importance of this organelle, the mechanisms that control cilium assembly as well as the precise requirements for cilia within tissues during adulthood are poorly understood.
We previously identified a kinase, Tau tubulin kinase 2 (TTBK2), as an essential component of a pathway that mediates cilium assembly. Moreover, this kinase is mutated a type of human hereditary ataxia, raising the possibility that some neurodegenerative conditions may result from ciliary dysfunction. Our research goals are to define pathways that control cilia assembly and to identify the requirements for cilia in the developing and adult nervous system, as well as in tissue homeostasis and repair more broadly.