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Professor ZHOU, Zhongjun 周中軍

Professor ZHOU, Zhongjun 周中軍

  • BSc (Xiamen U); MS, PhD (Peking Union Medical College); PhD (Karolinska Institutet)
  • Professor
L3-71, Laboratory Block, 21 Sassoon Road, Hong Kong
+852 3917 9542
+852 2855 1254
  • Aging, Chromatin Dynamics and Genomic maintenance
  • Stem cell self-renewal and differentiation in development, aging and cancer
  • Extracellular matrix and cell surface proteinases in regulation of growth factor signalling in development and diseases

Zhongjun Zhou is currently a professor at the School of Biomedical Sciences, The University of Hong Kong. He graduated from Xiamen University with a BSc in Biochemistry. He obtained Master of Science in Biochemistry and PhD in Pathophysiology from Peking Union Medical College. He also obtained a PhD degree in Medical Biochemistry from Karolinska Institute, Sweden. After postdoctoral training in in Karolinska Institute, he joined the department as a Research Assistant Professor in 2002 and became Associate Professor in 2005. He has published more than 40 original papers, reviews and book chapter. He is the co-founding Chair of Asian Association of Aging Research.

Prof Zhou is interested in understanding the biological functions of extracellular and nuclear matrix proteins. He works on signaling regulation in development, aging, and tumorigenesis using genetically modified mice and human patient tissues. He identified lamin A as the endogenous substrate of metalloproteinase Zmpste24 and demonstrated for the first time that genomic instability is behind the most severe human early aging disease, Hutchinson-Gilford Progeria Syndrome (HGPS). He has demonstrated that nuclear matrix is not simply a scaffold but a functional structure in regulating chromatin dynamics through modulating epigenetic factors, such as histone deacetylases and acetyltransferases. An example of Zhongjun’s work that breaks new ground in the science of aging is his recent demonstration of resveratrol’s activation of the longevity protein SIRT1. He demonstrated that lamin A is an endogenous activator of SIRT1 and mediates the activation of SIRT1 deacetylase activity by resveratrol. This important finding clears the cloud over resveratrol as the activator of SIRT1. His works on healthspan extension provide new hope for patients with HGPS and aging-associated diseases. He is a well recognized internationally in the field of biology of aging. He has also made significant contributions to the understanding of membrane-type 1 matrix metalloproteinase function in development and signaling. He demonstrated that MT1-MMP is the major negative Notch signaling regulator to maintain lymphocyte differentiation. In addition, he beautifully showed the cross-talk between ADAM and MMP in regulating FGFR2 signaling and osteogenesis. His recent work revealed MT1-MMP as an endogenous inhibitor of lymphangiogenesis.

  • Postdoctoral fellows or senior research associate position are available immediately in the area of (1) Neural stem cells and brain development; (2) DNA repair and/or aging; (3) epigenetics and chromatin remodeling.
  • Chromatin remodeling in aging and Cancer
  • MT1-MMP in development, growth factor signaling, neurogenesis, lymphangiogenesis, and tumorigenesis
  • Stem cell self-renewal in cancer and aging
  • UHRF1 in the regulation of epigenetics and tumorigenesis
  • Isthmin in development, signaling and tumorigenesis

 

Expt results

Laminopathy-based premature aging is a result of genomic instability caused by defective recruitment of DNA-damage checkpoint/repair proteins 10 minutes (left panel) and 12 hours (right panel) after DNA damage

Members of Zhou's lab
 
  1. L Osório, X Wu, L Wang, Z Jiang, C Neideck, G Sheng,  Z Zhou*. ISM1 regulates NODAL signaling and asymmetric organ morphogenesis during development. J Cell Biol. 2019; 218 (7). DOI: 10.1083/jcb.201801081. [Download PDF]
  2. S Ghosh, SK Wong, Z Jiang, B Liu, Y Wang, Q Hao, V Gorbunova, X Liu, and Z Zhou*. Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice. eLIFE 2018. DOI: https://doi.org/10.7554/eLife.32127.001. [Download PDF]
  3. T Li, L Wang, Y Du, S Xie, X Yang, F Lian, Z Zhou* and C Qian*. Structural and mechanistic insights into UHRF1-mediated DNMT1 activation in the maintenance DNA methylation. Nucleic Acids Research 2018. DOI: https://doi.org/10.1093/nar/gky104. [Download PDF]
  4. HL Wong, G Jin, R Cao, S Zhang, Y Cao, and Z Zhou*. MT1-MMP sheds LYVE-1 on lymphatic endothelial cells and suppresses VEGF-C production to inhibit lymphangiogenesis. Nature Communication 2016; 7:10824. doi: 10.1038/ncomms10824.
  5. S Ghosh, B Liu, Y Wang, Q Hao, and Z Zhou*. Lamin A is an endogenous SIRT6 activator and promote SIRT6-mediated DNA damage. Cell Reports 2015; 13(6): 1396–1406.
  6. B Liu, Z Wang, L Zhang, S Ghosh, H Zheng and Z Zhou*. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nature Communication 2013; 4:1868.
  7. B Liu, S Ghosh, X Yang, H Zheng, X Liu, Z Wang, B Zheng, B K Kennedy, Y Suh, M Kaeberlein, K Tryggvason, and Z Zhou*. Resveratrol rescues Sirt1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metabolism 2012; 16(6):738-750.
  8. K Chan, H Wong, G Jin, B Liu, R Cao, Y Cao, K Lehti, K Tryggvason and Z Zhou*. MT1-MMP Inactivates ADAM9 to Regulate FGFR2 Signalling in Calvarial Osteogenesis. Developmental Cell 2012; 22(6):1176-1190 (Faculty 1000, F1000 Factor 8.0).
  9. V Krishnan, MZ Chow, Z Wang, L Zhang, B Liu, X Liu and Z Zhou*. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Aca Sci USA 2011; 108 (30):12325-12330.
  10. G Jin, F Zhang, KM Chan, HL Wong, B Liu, KS Cheah, X Liu, C Mauch, D Liu, and Z Zhou*. MT1-MMP cleaves Dll1 to negatively regulate Notch signaling to maintain normal B cell development. EMBO J 2011; 30:2281–2293.
  11. B Liu, J Wang, KM Chan, WM Tjia, W Deng, X Guan, JD Huang, K M Li, PY Chau, DJ Chen, D Pei, AM Pendas, J Cadinanos, C Lopez-Otin, HF Tse, C Hutchison, J Chen, Y Cao, KS Cheah, K Tryggvason, and Z Zhou*. Genomic instability in laminopathy-based premature aging. Nature Medicine 2005; 11(7):780-785.
  12. A Pendás*, Z Zhou*, J Cadinanos, JM Freije, J Wang, K Hultenby, A Astudillo, A Wernerson, F Rodriguez, K Tryggvason, and C Lopez-Otin. Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase–deficient mice. Nature Genetics 2002; 31(1): 94-99. *Equal contribution
  13. Z Zhou, R Soininen, R Cao, GY Baaklini, RW Rauser, J Wang, Y Cao, and K Tryggvason. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci U S A 2000; 97(8):4052-4057.

*Corresponding author

  1. 2014 - 2017 RGC Collaborative Research Fund (CRF): Regulation of heterochromatin remodeling in DNA repair and aging.
  2. 2013 - 2016 RGC General Research Fund (GRF): Interplay between ADAM15 and MT1-MMP in FGF2-induced angiogenesis.
  3. 2011 - 2014 RGC General Research Fund (GRF): Isthmin In Fibroblast Growth Factor Signalling and Nodal Signalling during Embryogenesis and Development. (ongoing)
  4. 2013 - 2016 Shenzhen Science and Technology Bureau: Role for MT1-MMP in lymphoangiogenesis.
  5. 2013 - 2017 Natural Science Foundation of China (NSFC) Key Basic Research Program: Critical alterations in epigenetics and signalling pathways in accelerated aging.
  6. 2012 - 2016 Natural Science Foundation of China (NSFC) General Research Fund: MT1-MMP regulates neural stem cells self-renewal and differentiation via Notch signaling.
  • Croucher Senior Research Fellow 2015/2016, Croucher Foundation
  • Outstanding Research Award 2014/2015, The University of Hong Kong
  • State Science and Technology Award (2nd Class) 2011, State Council, China
  • International Society of Matrix Biology Nominated Speaker 2007, Cains, Australia
  • Outstanding Research Output Award 2006, Faculty of Medicine, The University of Hong Kong
  • Distinguished Overseas Young Chinese Scientist Award 2005, Natural Science Foundation of China
  • Young Investigator Award 2000, International Society of Fibrinolysis and Proteolysis, Japan
  • Swedish Cancer Foundation Fellow 1996-1997, Swedish Cancer Fond, Sweden
  • Associate Editor (Since 2015 Jan):
    Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis (Publisher: Elsevier B.V., Amsterdam; ISSN: 0027-5107, Impact Factor 4.44)
  • Member of Editorial Board (Since 2013):
    Clinical & Experimental Pharmacology & Physiology (Publisher: John Wiley & Sons Inc, Malden MA 02148, USA; Online ISSN: 1440-1681, Impact Factor 2.16)
  • Academic Editor (Since 2010):
    PLoS One (Publisher: Public Library of Science, San Francisco, USA; eISSN-1932-6203 Impact Factor 4.24)
  • Xuelai Wang, Senior research associate, PhD
  • Liliana Osorio, Postdoctoral fellow, PhD (Paris)
  • Xavier Wong Hoi Leong, Postdoctoral fellow, PhD (HKU)
  • Xi Yang, PhD student, BSc (Peking University)
  • Misty Shuo Zhang, PhD student, BSc (Zhejiang University)
  • Shrestha Ghosh, PhD student, BSc (India)
  • Helen Iok Lou Ieong, PhD student, BSc (Taiwan)
  • Fei Long, PhD student, BSc (Shanghai Jiaotong University)
  • Mia Xiaobin HU, Postdoc fellow, PhD (HKU)
  • Yukun Feng, MPhil student, BSc (University of Science and Technology of China)
  • Vaidehi Krishnan, Assistant Professor IMCB, Singapore
  • Baohua Liu, PhD (HKU); Professor, Shenzhen University
  • Le Zang, PhD (HKU); Postdoc in Harvard Medical School
  • Guoxiang Jin, PhD (HKU); Postdoc in MD Anderson Cancer Center, Houston
  • Jin Zhou, PhD (HKU); Shanghai
  • Zimei Wang, Research Associate; Professor, Shenzhen University
  • Grace C T Kong, Postdoc fellow; Roche, Hong Kong
  • Juergen Scharner, MPhil (HKU); University College London
  • Xuewei Wu, PhD (HKU); Postdoc in USA
  • Shuangcheng Zhou, MPhil (HKU); Shanghai