Christopher J. Westlake, Ph.D.
Dr. Westlake’s laboratory uses advanced fluorescence and electron microscopy imaging techniques, biochemical approaches and zebrafish models to investigate membrane trafficking processes regulated by the Rab small GTPase family that are important in development and disease. His current work focuses on a Rab11-Rab8 cascade which functions in primary cilium formation and apical membrane formation in polarized cells. His lab is also investigating the role of Rabs in the regulation of ciliary Hedgehog signaling. Defects in primary cilium formation and function are important in ciliopathy, diseases linked to primary cilia dysfunction, and cancer.
1) membrane trafficking, 2) Rab GTPases, 3) primary cilia, 4) ciliopathy, 5) superresolution microscopy, 6) Hedgehog signaling
My laboratory studies regulation of cellular membrane transport critical in development and normal homeostasis. Our focus has been on understanding the role of membrane trafficking regulators in ciliogenesis and ciliary signaling, including the Hedgehog pathway. Specifically, we are investigating the role of the Rab small GTPase family and associated trafficking regulators in the transport of membranes and signaling cargo at the cilium.
Using cell and zebrafish models along with cellular imaging, biochemistry and proteomics, and genetics systems we have discovered mechanisms for how ciliogenesis is initiated, characterized new regulators of cilium assembly, identified novel ciliary trafficking pathways, and connected these processes to human disorders and cancer. Our findings also provide insight into the basic biological processes of membrane trafficking that are affected in a wide range of human disease states.
For our cellular imaging studies, we utilize cutting-edge approaches including; live-cell and super resolution microscopy (SIM, STED, STORM), transmission electron microscopy, focused ion beam scanning electron microscopy (FIB-SEM), and correlative light and electron microscopy (CLEM).
The Membrane Trafficking and Signaling Section has an opening for an outstanding postdoctoral fellow and staff scientist to explore membrane trafficking function in organelle biogenesis and signaling using advanced cellular imaging approaches. Please send your C.V. and statement of interest to email@example.com
Selected Key Publications
- Dev Cell. Jul 22:50: 229-246, 2019. [ Journal Article ]
Investigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport.Nat Commun.. Jan 25:10: 428, 2019. [ Journal Article ]
In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations.Cell Rep. Jul 11: 20: 384-396, 2017. [ Journal Article ]
- Nat. Cell Biol. 17: 228-40, 2015. [ Journal Article ]
Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome.Proc. Natl. Acad. Sci. U.S.A. 108: 2759-64, 2011. [ Journal Article ]
In 2004, Dr. Westlake obtained his Ph.D. in Biochemistry under the supervision of Dr. Roger Deeley at Queen's University in Canada. While there, he investigated the structure/function and trafficking of multidrug resistance proteins (MRP) that are important in resistance to chemotherapeutics. He then joined Dr. Richard Scheller at Genentech as a postdoctoral fellow investigating membrane trafficking regulation by the Rab small GTPase family. In 2011, Dr. Westlake joined the Laboratory of Cell and Developmental Signaling at the Center for Cancer Research where he studies membrane trafficking pathways important in ciliopathy, diseases linked to primary cilia dysfunction, and cancer. He was awarded tenure from NIH in 2020.
|Quanlong Lu Ph.D.||Research Fellow|
|Sumeth Perera Ph.D.||Postdoctoral Fellow (Visiting)|
|Saurabh Shakya Ph.D.||Postdoctoral Fellow (Visiting)|
|Huijie Zhao Ph.D.||Postdoctoral Fellow (Visiting)|
CCR News, June 13, 2019
Akt protein kinase pathway regulates key step in the initiation of cilia formation