Time: July 13, 2017, 9:30 am
Venue: Academic Report Hall of Department of Biotechnology
Lecturer: Dr. MIAO Qing, Associate Professor of Medical College of Wisconsin; Guest Professor of The National Center for Nanoscience and Technology
Dr. Qing Miao, Associate Professor of Medical College of Wisconsin; Visiting Professor of National Center for Nanoscience and Technology. He obtained his PhD degree majored in physical chemistry from Dalian Institute of Chemical Physics, Chinese Academy of Sciences in 1995, obtained his PhD degree majored in biochemistry and molecular biology from Medical University of South Carolina in 2002. He worked in Dalian Institute of Chemical Physics as assistant professor from 1995-196. He carried out postdoctoral research in School of Medicine,Yale University from 2002-2006. He worked as associate research scientist in School of Medicine, Yale University from 2006 to 2007. He worked as assistant professor in Medical College of Wisconsin from 2007 to 2013. From 2013 to now, he worked as associate professor in Medical College of Wisconsin and visiting professor in key laboratory for biomedical effects of nanomaterials and nanosafety, National Center for Nanoscience and Technology.
His research is focused on the mechanism of the occurrence and development of vascular diseases and tumors as well as their biological therapy. He identified a new receptor for Nogo-B (NgBR) and further investigated its’ biological functions in blood vessel formation, hepatic lipogenesis and tumorigenesis. He has strong theoretical background and experiences in sample preparation and function analysis of proteins as well as the application of proteome technology in biological studies. He has received nearly $ 4 million funding from the National Institutes of Health (NIH) and undertaken a number of projects funded by the American Heart Association, the American Cancer Society and the Wisconsin Breast Cancer and Prostate Cancer Research Association. He has published 50 SCI articles, three patents and three review articles.
The localization of prenylatedRas at the plasma membrane promotes activation of Ras by receptor tyrosine kinases.Although Ras has been implicated in angiogenesis, the exact regulatory mechanisms controlling Ras translocation and activation are currently unclear. Nogo-B receptor (NgBR) was identified as a receptor specific for Nogo-B, a cell surface ligand involved in blood vessel remodeling. Our recent study demonstrated that NgBR has a conserved hydrophobic pocketthatpromotes the membrane accumulation of Ras by directly binding prenylatedRas at the plasma membrane.As we expected, NgBR knockdown in endothelial cells diminishes the membrane localization of Ras, and consequently abolishes VEGF/FGF-stimulated activation of Ras and Ras-mediated signaling such as phosphorylation of Akt and ERK. Therefore, NgBRknockout mouse isa unique animal model for examining the effects of Ras plasma membrane localization andRas signaling on the morphogenesis of endothelial cells. Genetic deletion of NgBR in endothelial cells results in embryonic lethality and dilated cerebral blood vessels with fewer pericytes, which resembles the vascular lesion happened in cerebral cavernous malformation(CCM). CCM is characterized by an abnormal cluster of enlarged blood vessels in the brain and spinal cord, and caused by dysfunction of three CCM genes (CCM1/2/3), which are required for maintaining endothelial cell (EC) junctions and pericyte recruitment. Our studies showed that NgBR transcript levels decrease in human CCM lesion, and NgBRendothelial specific knockout in mice results in decreased transcription of CCM1/2 in the yolk sac. Additional support for NgBR-CCM1/2 connections comes from studies using cultured human brain microvascular ECs, where loss of NgBR expression also decreases CCM1/2 transcriptionviaNgBR-mediated Ras pathway, which is required for the expression of key transcription factors that are involved in regulating transcription of CCM1/2 genes. Our findings suggest that NgBR-Ras signaling pathway regulates CCM1/2 expression, and that disrupting this signaling pathway results in cerebrovascular malformation.
Contact：Prof. ZHANG Lihua Group 1810