Zhang Ya'ou

    1991 Ph.D. West China University of Medical Sciences, Hematology/Oncology

    1986 M.S. West China University of Medical Sciences, Cardiovasology

    1982 M.D. West China University of Medical Sciences, Medicine

Dr. Ya-ou Zhang is a cellular and molecular biologist with a M.D. degree from the Medical school of West China University of Medical Sciences. As an attending physician, associate chief physician and associate professor, she worked for West China University of Medical Sciences from 1989 to 1994. She received her post-doctoral training at the University of Toronto, worked as a postdoctoral research fellow for Harvard Medical School and University of California at San Francisco, and as a researcher at City University of Hong Kong. 

Since 2004, she has joined Tsinghua Shenzhen International Graduate School (formerly Graduate school at Shenzhen, Tsinghua University). She is currently Professor, Deputy Director of Tsinghua University Open FIESTA Center, Director of the BIO3 Master's program, and Director of the Shenzhen Key Laboratory of Health Science and Technology

Member of a Council of Biochemical Association in Shenzhen.

Member of a Council of Biochemical Association in Shenzhen.

The functions and mechanism of noncoding RNA in tumor, neurodegenerative diseases and metabolic diseases.

Research and development of small nucleic acid drugs.

Science & Medicine;

    Advances in Molecular & Cell Biology;

    Introduction to Medicine

1. The functions and mechanism of noncoding RNA in tumor, neurodegenerative diseases and metabolic diseases.

2. Research and development of small nucleic acid drugs.

1. The functions and mechanism of noncoding RNA in tumor, neurodegenerative diseases and metabolic diseases.

2. Research and development of small nucleic acid drugs.

1.     National Natural Science Foundation of China “PGC-1β and its intronic miRNA regulate autophagy during adipocyte differentiation”, 31571400

2.     Basic research fund of Shenzhen, “The Study on the new mechanism of Warburg effect and the methods of Tumor therapy via inhibit Warburg effect”, JCYJ20170405103953336

3.     Basic research fund of Shenzhen, “The effect of Glial cell lesion related noncoding RNAs on Alzheimer disease” JCYJ20150724173156330

4.     Special project of Suzhou-Tsinghua innovation leading action,” Study on universal nucleic acid drugs for DNA virus”, 2016SZ0312

5.     “Study on the mechanism of b2m-mrna as noncoding RNA regulating the replication and reactivation of herpes simplex virus type I.” National Natural Science Foundation of China (31371315) NSFC,850,000￥, 2014.01-2017.12

 6.     “Study on the inhibition of DNA virus and virus related tumor by small nucleic acid.” International research fund of Shenzhen, (GJHZ20140416153718941 ),  500,000￥2014.01-2016.12

7.     “Effect of noncoding nucleic acids related to glial cytopathy on Alzheimer's disease and its mechanism” Basic research fund of Shenzhen (JCYJ20150724173156330), 3,000,000￥, 2015.10-2017.10

1.     Glycolipid metabolism and lysosomal cathepsins: 1) We reported that Cat L plays an important role in adipocyte differentiation and glycolipid metabolism. This report provided a new target for the treatment of obesity and diabetes mellitus. The paper is published in Nature Cell Biology. 2) We were able to prove that Cathepsins promoted the formation of atherosclerotic plaque. This study found a new target for the prevention and treatment of atherosclerosis. The paper is published in JCI.

2.     MicroRNA field: We reported that MiR-210 is up-regulated in multiple cancer types, and its up-regulation was highly correlated with the down-regulation of a group of mitosis-related genes. MiR-210 suppressed the expression of these genes by directly targeting their 3‘-UTRs. Exogenous miR210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. The paper was published in Nucleic Acids Res. I also found that MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway and published the paper in Autophagy.

3.     LncRNA Study: We focused on lncRNA study and found that lncRNA EPB41L4A-AS1 is p53 regulated lncRNA. Its expression was frequently down-regulated in a variety of human cancers and its low expression associated with poor prognosis of cancer patients. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. The paper was published in EBioMedicine. We also reported thatNEAT1 exhibits repressed expression in the early stage of AD patients. Its down-regulation declines neuroglial cell mediating Aβ clearance via inhibiting expression of endocytosis-related genes. The mechanism is related to NEAT1 mediated histone modification of H3K27Ac and H3K27Cro in these genes. This study is first to reveal the different roles of H3K27Ac and H3K27Cro in regulation of these gene expression and provides insight on the epigenetic regulatory mechanism of NEAT1 in gene expression and AD pathology  (Cell Mol Life Sci.).

4.     Drug Discovery Based on Small RNAs: We found several miRNAs which have close relationship with cancer from our basic research. Based on these miRNAs and other small RNAs, we began to engage in drug discovery work and obtained 8 Chinese patents. Our work was awarded with the National Major Projects Research Funds for innovation of new drug twice.

1. Liao W, Liu F, Zhang H, Liao W, Xu N, Xie W, Zhang Y*. Upregulation of GpncA is associated with poor prognosis through enhancement of tumor growth via regulating GSK3B. Sci Rep. 2020 Feb 6;10(1):2044. 

2. Liao M, Liao W, Xu N, Li B, Liu F, Zhang S, Wang Y, Wang S, Zhu Y, Chen D, Xie W, Jiang Y, Cao L, Yang BB, Zhang Y*. LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2. EBioMedicine. 2019 Mar;41:200-213

3. Wang Z, Zhao Y, Xu N, Zhang S, Wang S, Mao Y, Zhu Y, Li B, Jiang Y, Tan Y, Xie W, Yang BB, Zhang Y*. NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis-related genes expression. Cell Mol Life Sci. 2019 Aug;76(15):3005-3018.

4. Zhu Y, Liu Q, Liao M, Diao L, Wu T, Liao W, Wang Z, Li B, Zhang S, Wang S, Xie W, Jiang Y, Xu N, Zeng Y, Yang BB, Zhang Y*.. Overexpression of LncRNA EPB41L4A-AS1 induces metabolic reprogramming in trophoblast cells and placenta tissue of miscarriage. Mol Ther Nucleic Acids. 2019 Sep 26;18:518.

5. Liao M, Liu Q, Li B, Liao W, Xie W, Zhang Y. A group of long noncoding RNAs identified by data mining can predict the prognosis of lung adenocarcinoma. Cancer Sci. 2018 Oct 5. doi: 10.1111/cas.13822

6. Sun B, Fan P, Liao M, Zhang Y*. Modeling endophilin-mediated Aβ disposal in glioma cells. Biochim Biophys Acta. 2018 Jul 4;1865(10):1385-1396

7. Wang Z， Fan P，Zhao Y，Zhang S, Lu J, Xie W2, Jiang Y, Lei F, Xu N， Zhang Y. NEAT1 modulates herpes simplex virus-1 replication by regulating viral gene transcription. Cell Mol Life Sci. 2017 Mar;74(6):1117-1131

8. Liu L, He J, Wei X, Wan G, Lao Y, Xu W, Li Z, Hu H, Hu Z, Luo X, Wu J, Xie W, Zhang Y, Xu N. MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability. Oncogene. 2017 Oct 19;36(42):5874-5884.

9. Wang Z, Liu Q, Lu J, Fan P, Xie W1, Qiu W, Wang F, Hu G, Zhang Y. Serine/Arginine-rich Splicing Factor 2 Modulates Herpes Simplex Virus Type 1 Replication via Regulating Viral Gene Transcriptional Activity and Pre-mRNA Splicing. J Biol Chem. 2016 Dec 16;291(51):26377-26387

10. Wan G, Xie W, Liu Z, Xu W, Lao Y, Huang N, Cui K, Liao M, He J, Jiang Y, Yang BB, Xu H, Xu N, Zhang Y. Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy. 2014 Jan 1;10(1):70-9.

11. Wu J, Lv Q, He J, Zhang H, Mei X, Cui K, Huang N, Xie W, Xu N, Zhang Y.  MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes. Cell Commun Signal. 2014 Oct 11;12:66.

12. Zhao HJ, Ren LL, Wang ZH, Sun TT, Yu YN, Wang YC, Yan TT, Zou W, He J, Zhang Y, Hong J, Fang JYMiR-194 deregulation contributes to colorectal carcinogenesis via targeting AKT2 pathway. Theranostics. 2014 19;4(12):1193-208

13. He J, Wu J, Xu N, Xie W, Li M, Li J, Jiang Y, Yang BB*, Zhang Y*. MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes. Nucleic Acids Res. 1;41(1):498-508. 2013

14. Min Yang*, Yaou Zhang*, Jiehong Pan*, Jiusong Sun, Jian Liu, Peter Libby, Galina K. Sukhova, Alessandro Doria, Nobuhiko Katunuma, Odile D. Peroni, Michèle Guerre-Millo, Barbara B. Kahn, Karine Clement & Guo-Ping Shi. Cathepsin L activity controls adipogenesis and glucose tolerance. Nature Cell Biology. Nat Cell Biol. 2007 Aug;9(8):970-7. (Co-first author)

15. Sukhova GK*, Zhang Y* Pan JH, Wada Y, Yamamoto T, Naito M, Kodama T, Tsimikas S, Witztum JL, Lu ML, Sakara Y, Chin MT, Libby P, Shi GP. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2003 Mar;111(6):897-906 Co-first author)

1991 Ph.D. West China University of Medical Sciences, Hematology/Oncology

1986 M.S. West China University of Medical Sciences, Cardiovasology

1982 M.D. West China University of Medical Sciences, Medicine

Dr. Ya-ou Zhang is a cellular and molecular biologist with a M.D. degree from the Medical school of West China University of Medical Sciences. As an attending physician, associate chief physician and associate professor, she worked for West China University of Medical Sciences from 1989 to 1994. She received her post-doctoral training at the University of Toronto, worked as a postdoctoral research fellow for Harvard Medical School and University of California at San Francisco, and as a researcher at City University of Hong Kong. 

Since 2004, she has joined Tsinghua Shenzhen International Graduate School (formerly Graduate school at Shenzhen, Tsinghua University). She is currently Professor, Deputy Director of Tsinghua University Open FIESTA Center, Director of the BIO3 Master's program, and Director of the Shenzhen Key Laboratory of Health Science and Technology

• Overseas High-Caliber Personnel (Level B) in Shenzhen

• Selected as part of Shenzhen's Hundred People Plan