Center For Life Sciences

Location：Home - Principal Investigators

Ruiping XIAO

Ruiping XIAO

Email: xiaor(at)pku(dot)edu(dot)cn；

Telephone: +86-10-62757243；

Lab Homepage: http://www.imm.pku.edu.cn/news.php?id=29

Research Area:

Dr. Xiao has made important discoveries in beta-adrenergic receptor (AR) subtype signaling, with an emphasis on translating bench discoveries to the bedside. She was the first to show thatbeta2-AR dually couples to Gs and Gi, revealing a new signaling paradigm of the G protein-coupled receptor superfamily. While chronic beta1-AR stimulation causes heart cell death and cardiomyopathy by Ca2+/calmodulin kinase II-dependent pathways, beta2-AR is cardiac protective. She co-invented the Gs-biased, chiral beta2-AR agonist R,R-feneterol and co-supervised its Phase I clinical trial (Phase II planned), spearheading a novel therapy treating heart failure with beta2-AR agonist R,R-feneterol or derivatives combined with beta1-AR blocker. Her current research has revealed that MG53 E3 ligase-mediated, ubiquitin-dependent degradation of insulin receptor and insulin receptor substrate 1 constitutes a fundamental mechanism for the development of systemic insulin resistance, leading to the sequelae of metabolic syndrome and cardiovascular complications. She has authored >140 peer-reviewed publications. She has been global leader in biomedical research and served as the founding director of the Institute of Molecular Medicine, Peking University since 2005. She has also played a leadership role in clinical translational research and currently serves as an Associate Editor of The New England Journal of Medicine。

Selected Publications:

1. Zhu WZ, Zheng M, Koch WJ, Lefkowitz RJ, Kobilka BK, Xiao RP. Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes. Proc Nat Acad Sci USA. 98: 1607-1612, 2001.

2. Zhu WZ, Wang SQ, Chakir K, Yang D, Zhang T, Brown JH, Devic E, Kolbilka BK, Cheng H, Xiao RP. Linkage of β1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/Calmodulin Kinase II. J Clin Invest. 111: 617-625, 2003.

3. Xiao RP, Zhang SJ, Chakir K, Avdonin P, Zhu W, Bond RA, Balke CW, Lakatta EG, Cheng H. Enhanced Gi signaling selectively negates β1-AR but not β1-AR-mediated positive inotropic effect in myocytes from failing rat hearts. Circulation. 108: 1633-1639, 2003.

4. Song R, Peng W, Zhang Y, Lv F, Wu HK, Guo J, Cao Y, Pi Y, Zhang X, Jin L, Zhang M, Jiang P, Liu F, Meng S, Zhang X, Jiang P, Cao CM, Xiao RP. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Nature. 494: 375-379, 2013.

5. Liu F, Song R, Feng Y, Guo J, Chen Y, Zhang Y, Chen T, Wang Y, Huang Y, Li CY, Cao C, Zhang Y, Hu X, Xiao RP. Upregulation of MG53 induces diabetic cardiomyopathy through transcriptional activation of PPAR α. Circulation. 131: 795-804, 2015.

6. Zhang T, Zhang Y, Cui M, Jin L, Wang Y, Lv F, Liu Y, Zheng W, Shang H, Zhang J, Zhang M, Wu HK, Guo J, Zhang X, Hu X, Cao CM, Xiao RP. CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med. 22: 175-182, 2016.