Dr. Xuebiao Yao, University of Science & Technology of China--Molecular Delineation of Microtubule Dynamics in Mitosis

编辑: Date:2014/10/16

Xuebiao Yao, Ph.D.
Cheung Kong Professor
Director, Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, University of Science & Technology of China School of Life Sciences
 
Education and Appointment
January 2000�Present: Cheung Kong Professor, University of Science & Technology of China
January 1998�December 1999: Assistant Professor, University of Wisconsin�Madison, USA
June 1995�December 1997: Postdoctoral Associate, University of California�San Diego
January 1992�May 1995: Graduate Research Assistant, University of California�Berkeley
 
Research Interest & Achievements
We are interested in elucidating the molecular mechanisms in the regulation of assembly of microtubule plus�end regulation by post� ranslational modifications and cellular metabolisms. We have discovered the TIP150, a microtubule plus�end tracking protein essential for spindle orientation. We also identified a cooperative mechanism between CENP�E and SKAP in chromosome congression and central spindle establishment. Recently, we have revealed that EB1 acetylation by PCAF ensures accurate kinetochore–microtubule interactions in mitosis, suggesting dynamic acetylation of EB1 as a molecular mechanism to orchestrate accurate kinetochore–microtubule interactions in mitosis. These results establish a previously uncharacterized regulatory mechanism governing localization of microtubule plus�end tracking proteins and thereby the plasticity and dynamics of cells.

To visualize the spatiotemporal gradient post-ranslational modifying enzymatic
activities, we developed an expanded palette of genetically encoded indicators to report temporal dynamics of post-ranslational modifications such as phosphorylation, acetylation and methylation in centromere in real� ime mitosis. We demonstrated that the asymmetry of polarized epithelial is achieved with different isoforms of cytoplasmic actin and isoform�selective binding proteins. We discovered ACAP4, an ARF6 GTPase�activating protein and ARF6�ACAP4�ezrin signaling cascade in cell migration. The ARF6�ACAP4�ezrin signaling cascade links stimulus input at basolateral membrane, vesicular trafficking to apical membrane cytoskeletal remodeling. Most importantly, we had identified PITPNM3 as a receptor for relaying chemokine CCL18 effect in promoting breast cancer metastasis via ARF6�ACAP4�ezrin signaling axis. This finding demonstrated the feasibility of interrogation of ARF6�ACAP4—ezrin signaling as a viable therapy in prevention of breast cancer metastasis. Using a phenotyp-based screen of chemical library, he has identified a palette of small molecule chemical inhibitors for ACAP4. An extension of this approach is to accelerate the translational studies.