• Principal Investigator, Doctoral Advisor
• Institute of Molecular Medicine, College of Future Technology, Peking University
  National Biomedical Imaging Center
  Vice-Director, Non-human Primate Research Center

• 个人简介

  Main research directions:
  1. Establishment and study of animal models of metabolic and cardiovascular diseases in non-human primates;
  2. Study the pathogenesis of metabolic and cardiovascular diseases using non-human primate models;
  3. Pharmacodynamics studies using non-human primate models;
  4. Using rodent and non-human primates to study the role and mechanism of gut in obesity and metabolic diseases.
  
  Outstanding achievements:
  1. Innovative drug research and development: The original new drug, prolactin receptor monoclonal antibody, developed in cooperation with Bayer, Germany, has a significant effect on the model of spontaneous hair loss in red-faced monkeys. Currently, the antibody has completed phase I clinical trials and is undergoing global multicenter phase II clinical trials.
  2. Crack the mechanism of clinical drug action: The screening method and diagnostic criteria of rhesus monkey spontaneous hypertension were established. The rhesus monkey spontaneous hypertension model was used to monitor the blood pressure of awake animals for 24 hours with wireless telemetry technology. It was revealed that the improvement of the circadian rhythm of blood pressure induced by ipralidone treatment is the mechanism of reducing the cardiac and renal damage of hypertension, which has important significance for guiding clinical medication.
  3. New pathogenic genes found in Rhesus monkey family studies: It is expected to provide new strategies for the discovery of new targets for major diseases by using extreme phenotypes of monkeys as a breakthrough point to carry out family genetics studies. PRKD2 is a novel gene for hyperinsulinemia. And found that the monkey phenotype can be passed on to offspring.
  4. Establishment of rhesus monkey model of spontaneous metabolic syndrome and type 2 diabetes mellitus: Through large-scale screening and long-term follow-up study, the model of spontaneous metabolic syndrome and type 2 diabetes mellitus were established, and the screening and diagnostic criteria of spontaneous metabolic syndrome in rhesus monkey and the diagnostic criteria of obesity in rhesus monkey were first presented, and a series of disease mechanism studies were carried out. In addition, more than 10 years of longitudinal tracking data and a valuable tissue sample library have been accumulated.
  5. For the first time, live gene knockout in rhesus monkeys was carried out: PROTAC technology was used to successfully carry out the application of live gene knockout technology in primates, and the effect was stable and could be eluted, providing an important tool for gene function research in large animals.
  6. The Rhesus monkey rheumatoid arthritis model was established for the first time: The mouse induced arthritis model can only simulate human diseases in some aspects, but has significant differences from human diseases in pathogenesis, immune regulation and other aspects. The role of RIPK1-VDAC1 pathway in early myocardial injury associated with rheumatoid arthritis was first identified in rhesus monkey model of spontaneous rheumatoid arthritis.

• 所授课程

  Experimental Pathology (Elective, 2 credits)
  Obesity and Cardiovascular Disease (Elective, 2 credits)
  Disorders of Intestinal Function and Metabolism (Elective, 2 credits)

• 个人履历

  2021/04-now, PI, Institute of Molecular Medicine, Peking University, Non-human Primate Research Center, Pathology Experiment Center, Deputy Director, Engineering Research Center for Preclinical Primate and Large Animal Research, Ministry of Education
  2013/09-2021/03 PI, Institute of Molecular Medicine, Peking University, Non-human Primate Research Center, Pathology Experiment Center
  2006/03-2013/8, Associate PI, Institute of Molecular Medicine, Peking University, Co-PI, Non-human Primate Research Center, PI, Pathology Experiment Center
  2002/04-2006/02 Postdoctoral Fellow, Department of Molecular Biology and Pharmacology, University of Washington School of Medicine, USA
  1998/04-2002/03, Ph. D., Kumamoto University School of Medicine, Japan
  1997/04-1998/03, Division of Differentiation Control, Kumamoto University Medical College, Japan, Special Researcher, Ministry of Education, Japan (Lecturer with special attendance)
  1996/06-1997/03, Visiting PI, Department of Tumor Biology, Kumamoto University Medical College, Japan
  1995/07-1996/05, pathologist, Fuwai Hospital, Chinese Academy of Medical Sciences
  1992/09-1995/07, Master of Pathology, China Medical University

• 团队成员

  BAI Jieyingm, Researcher
  WANG Yu, Associate Researcher
  ZHENG Wen, Engineer
  YUAN Ye, Postdoctoral Fellow
  SUN Xueting, Secretary

• 承担项目

  1. National Key Research and Development Program, 2018YFA0801405, "Research on the Creation and Preclinical Treatment of Monkey Models of developmental and metabolic Complex Diseases with Targeted gene Editing", The Creation and preclinical research of primate models of developmental and metabolic complex Diseases, 2019.11 -- 2024.10, 8.64 million Yuan. Project leader
  2. National Natural Science Foundation of China, 81970690, "Protective effect of β-cell-specific RIPK1 knockout on impaired glucose tolerance in mice induced by high fat diet and its mechanism", 550,000 Yuan, 2020.01 -- 2023.12, Project Director
  3. National Key Research and Development Program, 2018YFA0507600, Chemical Labeling and Functional Regulation of protein glycoylation, 2018.05-2023.04, RMB 3.178,100, key participant
  Completed projects:
  1. National Natural Science Foundation of China, 81471063, "The role and mechanism of the proliferation of small intestinal epithelial cells mediated by Receptor Interacting Protein 1 (RIP1) in the development of obesity", January 2015 -- December 2018, 730,000 Yuan, Project leader
  2. Project 973, Ministry of Science and Technology, 2013CB531200, Research on Mechanism and Intervention Strategy of Early heart Failure caused by mitochondrial Dysfunction, 2013.1 -- 2017.12, RMB 2.18 million, backbone of the project
  3. National Natural Science Foundation of China, 81270883, Study on the mechanism of protein kinase D2 in the development of insulin resistance, 2013.1 -- 2016.12, 700,000 Yuan, Project leader
  4. New Drug Project 2013ZX09501014, Application of primate disease model in evaluation of early druggability, 2013.1-2016. 123.21 million Yuan, Project leader
  5. National Natural Science Foundation of China 30870996, Study on the function and mechanism of Leptin in gastrointestinal development, 2009.1 -- 2011.12, 300,000 Yuan, Project leader

• 代表性论文及论著

  1. Zhang X, Li D, Sun R, Hu X, Song Z, Ni X, Zhu H, Guo T, Qin C, Xiao RP. sRAGE alleviates SARS-CoV-2-induced pneumonia in hamster. Signal Transduct Target Ther. 2022 Feb 2;7(1):36.
  2. Zhu T, Lei M, Wang Z, Zhang R, Zhang Y, Jin W, Yu C, Huang CL, Liu D, Zheng W, Liu Y, Quan X, Kong L, Liang S, Zhang X*. A Comparative Study of Systolic and Diastolic Mechanical Synchrony in Canine, Primate, and Healthy and Failing Human Hearts. Front Cardiovasc Med. 2021 Oct 28;8:750067.
  3. Wang C, Xiao Y, Wang J, Hou N, Cui W, Hu X, Zeng F, Yuan Y, Ma D, Sun X, Zhang Y, Zheng W, Liu Y, Shang H, Chen L, Xiao RP*, Zhang X*. Dynamic Changes in Insulin and Glucagon During Disease Progression in Rhesus Monkeys with Obesity-Related Type 2 Diabetes Mellitus. Diabetes Obes Metab. 21:1111-1120, 2019.
  4. Sun X, Wang J, Yao X, Zheng W, Mao Y, Lan T, Wang L, Sun Y, Zhang X, Zhao Q, Zhao J, Xiao RP, Zhang X*, Ji G*, Rao Y*. A chemical approach for global protein knockdown from mice to non-human primates. Cell Discov. 2019, 5:10.
  5. Zeng F, Wen W, Cui W, Zheng W, Liu Y, Sun X, Hou N, Ma D, Yuan Y, Shi H, Wang Z, Li Z, Xiao Y, Wang C, Li Y, Shang H, Li CY, Wang J, Zhang Y, Xiao R-P*, Zhang X*. Central role of RIPK1-VDAC1 pathway on cardiac impairment in a non-human primate model of rheumatoid arthritis. J Mol Cell Cardiol. 125:50-60, 2018.
  6. Zheng W, Liu Y, Shang H, Zhang Y, Ma D, Hou N, Wang J, Sun X, Peng Y, Pan L, Wang Z, Tang X, Xiao R‑P, Zhang X*. Characterization of spontaneously developed non-alcoholic fatty liver disease in aged rhesus monkeys. Diabetol Metab Syndr. 10:68, 2018.
  7. Xiao Y, Wang C, Chen JY, Lu F, Wang J, Hou N, Hu X, Zeng F, Ma D, Sun X, Ding Y, Zhang Y, Zheng W, Liu Y, Shang H, Zhu W, Han C, Zhang Y, Ouyang K, Chen L, Chen J, Xiao RP, Li CY*, Zhang X*. Deficiency of PRKD2 triggers hyperinsulinemia and metabolic disorders. Nat Commun. 9:2015, 2018.
  8. Zeng F, Chen X, Cui W, Wen W, Lu F, Sun X, Ma D, Yuan Y, Li Z, Hou N, Zhao H, Bi X, Zhao J, Zhou J, Zhang Y, Xiao RP, Cai J*, Zhang X*. RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis. Cancer Res. 78:2876-2885, 2018.
  9. Zhang Y, Zheng W, Liu Y, Wang J, Peng Y, Shang H, Hou N, Hu X, Ding Y, Xiao Y, Wang C, Zeng F, Mao J, Zhang J, Ma D, Sun X, Li C, Xiao RP*, Zhang X*. Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome. Sci Rep. 6:23957, 2016.
  10. Ding Y, Fang H, Shang W, Xiao Y, Sun T, Hou N, Pan L, Sun X, Ma Q, Zhou J, Wang X, Zhang X*, Cheng H. Mitoflash altered by metabolic stress in insulin-resistant skeletal muscle. J Mol Med (Berl). 93:1119-30, 2015.
  11. Chen JY, Peng Z, Zhang R, Yang XZ, Tan BC, Fang H, Liu CJ, Shi M, Ye ZQ, Zhang YE, Deng M, Zhang X*, Li CY*. RNA editome in rhesus macaque shaped by purifying selection. PLoS Genet. 10:e1004274, 2014.
  12. Mao J, Hu X, Xiao Y, Yang C, Ding Y, Hou N, Wang J, Cheng H, Zhang X*. Overnutrition stimulates intestinal epithelium proliferation through β-catenin signaling in obese mice. Diabetes. 62:3736-46, 2013.
  13. Zhang SJ, Liu CJ, Shi M, Kong L, Chen JY, Zhou WZ, Zhu X, Yu P, Wang J, Yang X, Hou N, Ye Z, Zhang R, Xiao R, Zhang X*, Li CY*. RhesusBase: a knowledgebase for the monkey research community. Nucleic Acids Res. 41(Database issue):D892-905, 2013.
  14. Zhang X, Zhang R, Raab S, Zheng W, Wang J, Liu N, Zhu T, Xue L, Song Z, Mao J, Li K, Zhang H, Zhang Y, Han C, Ding Y, Wang H, Hou N, Liu Y, Shang S, Li C, Sebokova E, Cheng H*, Huang PL. Rhesus macaques develop metabolic syndrome with reversible vascular dysfunction responsive to pioglitazone. Circulation. 124:77-86, 2011.