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  English.dicp.cas.cn    Posted:2013-07-01
Roles of Nogo-B receptor in regulating lipid metabolism in liver

Time: 2013-7-2 14:00

Location:Academic Hall of Bio-tech Building

Lecturer:Qing (Robert) Miao PhD

Professor, Medical College of Wisconsin, USA

Abstract:

Nogo-B was previously identified as a protein that is highly expressed in endothelial cells (EC) and vascular smooth muscle cells. Nogo-B receptor (NgBR) is a type I receptor, which was identified as a receptor specific for Nogo-B. Previously, we reported that NgBR expression is necessary for Nogo-B induced morphogenesis of endothelial cells as well as NPC2 dependent cholesterol trafficking in vitro. We demonstrated that NgBR deficiency leads to a decrease in NPC2 level and increases intracellular cholesterol accumulation under serum-free condition. Thus, it implies that NgBR may play a key role in regulating lipid metabolism and homeostasis. Here, we continue to investigate the role of NgBR in regulating hepatic lipid metabolism and steatosis under serum presence condition. Our groups discovered that NgBR is highly expressed in mouse liver. Our preliminary results showed that NgBR knockdown does not decrease either NPC2 levels or NPC2-depedent intracellular cholesterol amount in hepatocyte under serum presence condition. However, we found that NgBR knockdown results in significant increase of free fatty acid and triglyceride in hepatocyte in vitro and in vivo. Our results suggest that NgBR also have NPC2-indenpent role for lipid metabolism in hepatocytes. Furthermore, we found NgBR knockdown increases the translocation of LXRa into nuclei. Liver X receptor lpha(LXRa) is a member of nuclear receptor superfamily and one of master regulators for cholesterol and lipid metabolism. Real-time PCR results further showed that NgBR knockdown increased expression of LXRa-regulated gene such as ABCA1, ABCG5, ABCG8, SREBP1, FAS and PPARg, which are involved in lipid efflux and metabolism. We further demonstrated the mechanism by which NgBR promotes the activation of LXRa and effects of NgBR-regulated lipid metabolism in liver. These preliminary results suggest that LXRa translocation into nuclei is critical for NgBR-regulated lipid metabolism and hemostasis in liver, which may attribute to atherosclerosis.

Introduction:

EDUCATION:

9/1986 – 6/1990 BS, Zhejiang University, Hangzhou, China

9/1990 – 6/1995 PhD, Dalian Institute of Chemical Physics, Chinese Academy of Sciences,   Dalian, China

9/1997 – 6/2002 PhD, Medical University of South Carolina, Charleston, SC

POSTGRADUATE TRAINING AND FELLOWSHIP APPOINTMENTS:

9/2002 – 7/2006 Postdoctoral Fellow, Department of Pharmacology, Boyer Center for Molecular  

Medicine, Yale University School of Medicine, New Haven, CT

FACULTY APPOINTMENTS:

7/1995 – 6/1996  Assistant Professor, State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

7/2006 – 12/2007 Associate Research Scientist, Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT

12/2007 – 04/2013 Assistant Professor, Department of Surgery (Primary) and Department of Pathology, Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI

2/2008 – 04/2013 Assistant Professor (adjunct appointment), Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI

04/2013 - Present Associate Professor, Department of Surgery (Primary) and Department of Pathology, Children’s Research Institute, Medical College of Wisconsin,Milwaukee, WI

AWARDS AND HONORS:

5/1996 The President's Award of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China

1/1999 Albert Krall Memorial Award, South Carolina Statewide Research Conference on Molecular Approaches to Biological Problems

11/1999 First Place in the PhD III Poster Presentation Section, Medical University of South Carolina

9/2006  ATVB Conference Merit Award for Young Investigators, American Heart Association’s Council on Arteriosclerosis, Thrombosis, and Vascular Biology

1/2007 Scientist Development Awards, American Heart Association National Program

4/2010 ATVB Conference Merit Award for Young Investigators, American Heart Association’s Council on Arteriosclerosis, Thrombosis, and Vascular Biology

11/2010 Best of AHA Specialty Conferences at Scientific Sessions

8/2012 Young Investigator Award, 5th Mayo Clinic Angiogenesis Symposium

MEMBERSHIPS IN HONORARY AND PROFESSIONAL SOCIETIES:

1999 - 2007 American Chemical Society (Member)

2005 American Heart Association/American Stroke Association (Member)

2006 American Association for the Advancement of Science (Member)

2010 North American Vascular Biology Organization (Member)

2011 American Association for Cancer Research (Member)

2011 Medical College of Wisconsin Cancer Center (Member)

EDITORSHIPS/EDITORIAL BOARDS/JOURNAL REVIEWS:

Journal Review

2008 - Present Arteriosclerosis, Thrombosis, and Vascular Biology

2009 - Present Cancer Investigation

2010 - Present Blood

2011- Present PLoS ONE

2013- Present Nature Scientific Reports

Contact:1809 Lu Wang(9620)

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