Dr Chao Zhao University positionAssistant Director of Research Dr Chao Zhao is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Clinical Neurosciences Home pagehttp://www.vet.cam.ac.uk/researc... Research ThemesInterestsMy research focuses on mechanism of remyelination of central nervous system following demyelination in various conditions. After demyelinating injury, the system activates a repair process, which involves oligodendrocyte progenitor cells turning into mature myelinating oligodendrocytes to replace the lost myelin sheath of the axons. Failure of this process can result in axonal loss and permanent functional deficits, as seen in diseases such as multiple sclerosis. Understanding the remyelination process, including the regulating factors in injury environment and the cell's intrinsic properties is essential for developing means of enhancing the repair of normally non-repairable clinical conditions. In addition, study of this fine example of involvement of adult stem cells (precursor cells) in repair process is of general interest in regeneration biology. We combine molecular and cellular techniques, genetic approaches and in vivo demyelinating models to dissect this complicated process. Research Focus
EquipmentCalcium imaging Electron microscopy In situ hybridisation CollaboratorsNo collaborators listed Associated News ItemsKey publicationsFancy SP, Baranzini SE, Zhao C, Yuk DI, Irvine KA, Kaing S, Sanai N, Franklin RJ, Rowitch DH (2009), “Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.” Genes Dev 23(13):1571-85 Details Zhao C, Fancy SP, Franklin RJ, ffrench-Constant C (2009), “Up-regulation of oligodendrocyte precursor cell alphaV integrin and its extracellular ligands during central nervous system remyelination.” J Neurosci Res 87(15):3447-55 Details Zhao C, Fancy SP, ffrench-Constant C, Franklin RJ (2008), “Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination.” Neurobiol Dis 31(2):209-17 Details Zhao C, Li W-W, Franklin RJM (2006), “Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination” Neurobiol Aging 27(9):1298-307 Arnett HA, Fancy SPJ, Alberta JA, Zhao C, Plant SR, Som S, Raine CS, Rowitch D, Franklin RJM, Stiles CD (2004), “The bHLH transcription factor Olig1 is required for repair of demyelinated lesions in the CNS” Science 306(5704):2111-2115 Fancy SP, Zhao C, Franklin RJ (2004), “Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS” Molecular and Cellular Neuroscience 27(3):247-54 Details Publications2014Mei F, Fancy SP, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA, Etxeberria A, Xiao L, Franklin RJ, Green A, Hauser SL, Chan JR (2014), “Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.” Nat Med 20(8):954-60 Details Stoffels JM, Hoekstra D, Franklin RJ, Baron W, Zhao C (2014), “The EIIIA domain from astrocyte-derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination.” Glia Details Tyzack GE, Sitnikov S, Barson D, Adams-Carr KL, Lau NK, Kwok JC, Zhao C, Franklin RJ, Karadottir RT, Fawcett JW, Lakatos A (2014), “Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression.” Nat Commun 5:4294 Details 2013Coutts DJ, Humphries CE, Zhao C, Plant GW, Franklin RJ (2013), “Embryonic-derived olfactory ensheathing cells remyelinate focal areas of spinal cord demyelination more efficiently than neonatal or adult-derived cells.” Cell Transplant 22(7):1249-61 Details Stoffels JM, de Jonge JC, Stancic M, Nomden A, van Strien ME, Ma D, Sisková Z, Maier O, Ffrench-Constant C, Franklin RJ, Hoekstra D, Zhao C, Baron W (2013), “Fibronectin aggregation in multiple sclerosis lesions impairs remyelination.” Brain 136(Pt 1):116-31 Details Syed YA, Baer A, Hofer MP, González GA, Rundle J, Myrta S, Huang JK, Zhao C, Rossner MJ, Trotter MW, Lubec G, Franklin RJ, Kotter MR (2013), “Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination.” EMBO Mol Med 5(12):1918-34 Details Yuen TJ, Johnson KR, Miron VE, Zhao C, Quandt J, Harrisingh MC, Swire M, Williams A, McFarland HF, Franklin RJ, Ffrench-Constant C (2013), “Identification of endothelin 2 as an inflammatory factor that promotes central nervous system remyelination.” Brain 136(Pt 4):1035-47 Details 2012Chong SY, Rosenberg SS, Fancy SP, Zhao C, Shen YA, Hahn AT, McGee AW, Xu X, Zheng B, Zhang LI, Rowitch DH, Franklin RJ, Lu QR, Chan JR (2012), “Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination.” Proc Natl Acad Sci U S A 109(4):1299-304 Details Hampton DW, Innes N, Merkler D, Zhao C, Franklin RJ, Chandran S (2012), “Focal immune-mediated white matter demyelination reveals an age-associated increase in axonal vulnerability and decreased remyelination efficiency.” Am J Pathol 180(5):1897-905 Details Huang JK, Ferrari CC, Monteiro de Castro G, Lafont D, Zhao C, Zaratin P, Pouly S, Greco B, Franklin RJ (2012), “Accelerated axonal loss following acute CNS demyelination in mice lacking protein tyrosine phosphatase receptor type Z.” Am J Pathol 181(5):1518-23 Details 2011Fancy SP, Harrington EP, Yuen TJ, Silbereis JC, Zhao C, Baranzini SE, Bruce CC, Otero JJ, Huang EJ, Nusse R, Franklin RJ, Rowitch DH (2011), “Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination.” Nat Neurosci Details Huang JK, Fancy SP, Zhao C, Rowitch DH, Ffrench-Constant C, Franklin RJ (2011), “Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.” Neurotherapeutics 8(4):650-8 Details Huang JK, Jarjour AA, Nait Oumesmar B, Kerninon C, Williams A, Krezel W, Kagechika H, Bauer J, Zhao C, Evercooren AB, Chambon P, Ffrench-Constant C, Franklin RJ (2011), “Retinoid X receptor gamma signaling accelerates CNS remyelination.” Nat Neurosci 14(1):45-53 Details Zambonin JL, Zhao C, Ohno N, Campbell GR, Engeham S, Ziabreva I, Schwarz N, Lee SE, Frischer JM, Turnbull DM, Trapp BD, Lassmann H, Franklin RJ, Mahad DJ (2011), “Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis.” Brain 134(Pt 7):1901-13 Details 2010Barraud P, He X, Zhao C, Caldwell MA, Franklin RJ (2010), “FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures.” Exp Cell Res 316(9):1489-99 Details Bruce CC, Zhao C, Franklin RJ (2010), “Remyelination - An effective means of neuroprotection.” Horm Behav 57(1):56-62 Details Fancy SP, Kotter MR, Harrington EP, Huang JK, Zhao C, Rowitch DH, Franklin RJ (2010), “Overcoming remyelination failure in multiple sclerosis and other myelin disorders.” Exp Neurol Details Harrington EP, Zhao C, Fancy SP, Kaing S, Franklin RJ, Rowitch DH (2010), “Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination.” Ann Neurol 68(5):703-16 Details Zawadzka M, Rivers LE, Fancy SP, Zhao C, Tripathi R, Jamen F, Young K, Goncharevich A, Pohl H, Rizzi M, Rowitch DH, Kessaris N, Suter U, Richardson WD, Franklin RJ (2010), “CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination.” Cell Stem Cell 6(6):578-90 Details 2008Chandran S, Hunt D, Joannides A, Zhao C, Compston A, Franklin RJ (2008), “Myelin repair: the role of stem and precursor cells in multiple sclerosis.” Philos Trans R Soc Lond B Biol Sci 363(1489):171-83 Details Zhao C, Zawadzka M, Roulois AJ, Bruce CC, Franklin RJ (2008), “Promoting remyelination in multiple sclerosis by endogenous adult neural stem/precursor cells: defining cellular targets.” J Neurol Sci 265(1-2):12-6 Details 2007Barraud P, He X, Zhao C, Ibanez C, Raha-Chowdhury R, Caldwell MA, Franklin RJ (2007), “Contrasting effects of basic fibroblast growth factor and epidermal growth factor on mouse neonatal olfactory mucosa cells.” Eur J Neurosci 26(12):3345-57 Details Roulois AJ, Zhao C, Zawadzka M, Bruce CC, Franklin RJ (2007), “[Promoting remyelination in multiple sclerosis by endogenous adult neural stem/precursor cells]” Rev Neurol (Paris) 163(6-7):667-71 Details 2006Chari DM, Zhao C, Kotter MR, Blakemore WF, Franklin RJ (2006), “Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system.” J Neurosci Res 83(4):594-605 Details Kotter MR, Li WW, Zhao C, Franklin RJ (2006), “Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation.” J Neurosci 26(1):328-32 Details Li WW, Penderis J, Zhao C, Schumacher M, Franklin RJ (2006), “Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS.” Exp Neurol 202(1):250-4 Details Setzu A, Lathia JD, Zhao C, Wells K, Rao MS, Ffrench-Constant C, Franklin RJ (2006), “Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells.” Glia 54(4):297-303 Details Zhao C, Li WW, Franklin RJ (2006), “Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination.” Neurobiol Aging 27(9):1298-307 Details 2005Kotter MR, Zhao C, van Rooijen N, Franklin RJ (2005), “Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression.” Neurobiol Dis 18(1):166-75 Details Li WW, Setzu A, Zhao C, Franklin RJ (2005), “Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination.” J Neuroimmunol 158(1-2):58-66 Details Zhao C, Fancy SP, Kotter MR, Li WW, Franklin RJ (2005), “Mechanisms of CNS remyelination--the key to therapeutic advances.” J Neurol Sci 233(1-2):87-91 Details Zhao C, Fancy SP, Magy L, Urwin JE, Franklin RJ (2005), “Stem cells, progenitors and myelin repair.” J Anat 207(3):251-8 Details 2004Arnett HA, Fancy SP, Alberta JA, Zhao C, Plant SR, Kaing S, Raine CS, Rowitch DH, Franklin RJ, Stiles CD (2004), “bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS.” Science 306(5704):2111-5 Details 2003Zhao C, Strappe PM, Lever AM, Franklin RJ (2003), “Lentiviral vectors for gene delivery to normal and demyelinated white matter.” Glia 42(1):59-67 Details 2002Franklin RJ, Zhao C, Sim FJ (2002), “Ageing and CNS remyelination.” Neuroreport 13(7):923-8 Details Sim FJ, Zhao C, Li WW, Lakatos A, Franklin RJ (2002), “Expression of the POU-domain transcription factors SCIP/Oct-6 and Brn-2 is associated with Schwann cell but not oligodendrocyte remyelination of the CNS.” Mol Cell Neurosci 20(4):669-82 Details Sim FJ, Zhao C, Penderis J, Franklin RJ (2002), “The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation.” J Neurosci 22(7):2451-9 Details |