Faculty of Biological Sciences

Dr Jessica Kwok

PhD
University Academic Fellow in Medical Engineering in the Spinal Cord
School of Biomedical Sciences

Background: A neuro-/glyco-biologist focusing on enhancing plasticity for CNS pathologies. BSc in Biochemistry - University of Hong Kong (Hong Kong). PhD in Biochemistry - University of Hong Kong (Hong Kong). Postdoctoral scientist - University of Cambridge (UK). Visiting scientist - University of Grenoble Alpes (France).

Contact:  Garstang 5.55f, +44(0) 113 34 39802, email address for  

Research Interests

The role of chondroitin sulphates and perineuronal nets in spinal cord injury and memory

 

We aim to decipher the role of chondroitin sulphates (CSs) for a multitude of pathologies in the central nervous system (CNS), including spinal cord injury, ageing, memory and neurodegeneration.

Chondroitin sulphates in the central nervous system

Chondroitin sulphates belong to the family of glycosaminoglycans (GAGs). CSs are covalently bound to a core proteoglycans forming chondroitin sulphate proteoglycans (CSPGs), which are abundant in cartilage and CNS. In the CNS, CSPGs are strongly up-regulated after spinal cord injury in a structure called glial scar. Removal of CSs in the glial scar promotes neuronal regeneration.

CS in the perineuronal nets 

CS, apart from being strongly up-regulated after CNS injury, are also present in a structure called perineuronal nets (PNNs). PNNs are a layer of aggregated extracellular matrix, composed of CSPGs, link proteins and hyaluronan wrapping around the surface of sub-populations of neurons. Emerging evidence demonstrated that PNNs are important in controlling plasticity during development and regeneration. My research is mainly focused on understanding the structure of the PNNs, how they control plasticity and how to improve plasticity by PNN manipulation.             

 

 The Compositions and binding partners of PNNs

molecular composition of PNNs controls their properties, functions and binding partners. We have previously shown that the sulphation pattern of CSs in the PNNs is different from the pattern in the general brain extracellular matrix. CS-E isoforms are enriched in the PNN structure and controls the binding of semaphorin 3A to neurons. Semaphorin 3A is a repulsive guidance molecule, and its binding to PNN potentiate the inhibitory nature of PNNs.             

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Projects in all of the above areas are available. Enthusiastic and committed students are encouraged to contact me via email: j.kwok@leeds.ac.uk

Postgraduate studentship areas:

  • Enthusiastic and committed students are encouraged to contact me via email: j.kwok@leeds.ac.uk

See also:

Modules taught

BIOL5294M - MSc Bioscience Research Project Proposal
BIOL5392M - Bioscience MSc Research Project
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC3301 - Research Project in Biomedical Sciences
BMSC5301M - Advanced Research Topics

Group Leader Dr Jessica Kwok  (University Academic Fellow in Medical Engineering in the Spinal Cord)

The role of chondroitin sulphates and perineuronal nets in spinal cord injury and memory 

Dr Sylvain Gigout  (Research Fellow)

Postgraduates

Stuart Dickens (Primary supervisor) 60% FTE
Ashleigh Goodenough (Primary supervisor) 34% FTE
Sian Irvine (Primary supervisor) 90% FTE
Luke Souter (Primary supervisor) 50% FTE
Natalie Doody (Co-supervisor) 33% FTE
Roxanne Dyer (Co-supervisor) 20% FTE
Nicole Smith (Co-supervisor) 33% FTE
Katherine Timms (Co-supervisor) 13% FTE

Yang S, Hilton S, Alves JN, Saksida LM, Bussey T, Matthews RT, Kitagawa H, Spillantini MG, Kwok JCF, Fawcett JW Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration Neurobiology of Aging 59 197-209, 2017
DOI:10.1016/j.neurobiolaging.2017.08.002
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Kempf A, Boda E, Kwok JCF, Fritz R, Grande V, Kaelin AM, Ristic Z, Schmandke A, Schmandke A, Tews B, Fawcett JW, Pertz O, Buffo A, Schwab ME Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction Developmental Cell 43 24-34.e5, 2017
DOI:10.1016/j.devcel.2017.08.014
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Koseki H, Donegá M, Lam BYH, Petrova V, van Erp S, Yeo GSH, Kwok JCF, Ffrench-Constant C, Eva R, Fawcett JW Selective rab11 transport and the intrinsic regenerative ability of CNS axons eLife 6 -, 2017
DOI:10.7554/eLife.26956
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Kwok J Perineuronal nets: from molecular assembly to plasticity enhancement, 2017

van 't Spijker HM, Kwok JCF, Fawcett JW Neuronal pentraxin 2 binds to the perineuronal nets via hyaluronan, 2017

Djerbal L, Lortat-Jacob H, Kwok J Chondroitin sulfates and their binding molecules in the central nervous system Glycoconjugate Journal 34 363-376, 2017
DOI:10.1007/s10719-017-9761-z
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Foscarin S, Raha-Chowdhury R, Fawcett JW, Kwok JCF Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory Aging 9 1607-1622, 2017
DOI:10.18632/aging.101256
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Sorg BA, Berretta S, Blacktop JM, Fawcett JW, Kitagawa H, Kwok JCF, Miquel M Casting a wide net: Role of perineuronal nets in neural plasticity Journal of Neuroscience 36 11459-11468, 2016
DOI:10.1523/JNEUROSCI.2351-16.2016
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de Winter F, Kwok JCF, Fawcett JW, Vo TT, Carulli D, Verhaagen J The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity Neural Plasticity 2016 -, 2016
DOI:10.1155/2016/3679545
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Carulli D, Kwok JCF, Pizzorusso T Perineuronal Nets and CNS Plasticity and Repair Neural Plasticity 2016 -, 2016
DOI:10.1155/2016/4327082

Smith PD, Coulson-Thomas VJ, Foscarin S, Kwok JCF, Fawcett JW "GAG-ing with the neuron": The role of glycosaminoglycan patterning in the central nervous system Experimental Neurology 274 100-114, 2015
DOI:10.1016/j.expneurol.2015.08.004
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Heller JP, Kwok JCF, Vecino E, Martin KR, Fawcett JW A Method for the Isolation and Culture of Adult Rat Retinal Pigment Epithelial (RPE) Cells to Study Retinal Diseases Frontiers in Cellular Neuroscience 9 -, 2015
DOI:10.3389/fncel.2015.00449
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Tan CL, Kwok JCF, Heller JPD, Zhao R, Eva R, Fawcett JW Full length talin stimulates integrin activation and axon regeneration Molecular and Cellular Neuroscience 68 1-8, 2015
DOI:10.1016/j.mcn.2015.03.011
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Rowlands D, Sugahara K, Kwok JCF Glycosaminoglycans and glycomimetics in the central nervous system Molecules 20 3527-3548, 2015
DOI:10.3390/molecules20033527
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Kwok JCF, Foscarin S, Fawcett JW Perineuronal nets: A special structure in the central nervous system extracellular matrix In Extracellular Matrix , 2014
DOI:10.1007/978-1-4939-2083-9_3
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Tyzack GE, Sitnikov S, Barson D, Adams-Carr KL, Lau NK, Kwok JC, Zhao C, Franklin RJM, Karadottir RT, Fawcett JW, Lakatos A Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression Nature Communications 5 -, 2014
DOI:10.1038/ncomms5294
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Moshayedi P, Ng G, Kwok JCF, Yeo GSH, Bryant CE, Fawcett JW, Franze K, Guck J The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system Biomaterials 35 3919-3925, 2014
DOI:10.1016/j.biomaterials.2014.01.038
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Kwok JCF, Yang S, Fawcett JW Neural ECM in regeneration and rehabilitation Progress in Brain Research 214 179-192, 2014
DOI:10.1016/B978-0-444-63486-3.00008-6
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Kwok JCF, Heller JP, Zhao RR, Fawcett JW Targeting inhibitory chondroitin sulphate proteoglycans to promote plasticity after injury Methods in Molecular Biology 1162 127-138, 2014
DOI:10.1007/978-1-4939-0777-9_10
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Foscarin S, Fawcett JW, Kwok JCF Involvement of perineuronal nets and glycosaminoglycans in neuronal plasticity and ageing, 2013

Dick G, Liktan C, Alves JN, Ehlert EME, Miller GM, Hsieh-Wilson LC, Sugahara K, Oosterhof A, Van Kuppevelt TH, Verhaagen J, Fawcett JW, Kwok JCF Semaphorin 3A binds to the perineuronal nets via chondroitin sulfate type E motifs in rodent brains Journal of Biological Chemistry 288 27384-27395, 2013
DOI:10.1074/jbc.M111.310029
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Vo T, Carulli D, Ehlert EME, Kwok JCF, Dick G, Mecollari V, Moloney EB, Neufeld G, de Winter F, Fawcett JW, Verhaagen J The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain Molecular and Cellular Neuroscience 56 186-200, 2013
DOI:10.1016/j.mcn.2013.04.009
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Vorobyov V, Kwok JCF, Fawcett JW, Sengpiel F Effects of digesting chondroitin sulfate proteoglycans on plasticity in cat primary visual cortex Journal of Neuroscience 33 234-243, 2013
DOI:10.1523/JNEUROSCI.2283-12.2013
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Tan CL, Andrews MR, Kwok JCF, Heintz TGP, Gumy LF, Fässler R, Fawcett JW Kindlin-1 enhances axon growth on inhibitory chondroitin sulfate proteoglycans and promotes sensory axon regeneration Journal of Neuroscience 32 7325-7335, 2012
DOI:10.1523/JNEUROSCI.5472-11.2012
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Kwok JCF, Warren P, Fawcett JW Chondroitin sulfate: A key molecule in the brain matrix International Journal of Biochemistry and Cell Biology 44 582-586, 2012
DOI:10.1016/j.biocel.2012.01.004
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Kwok JCF, Yuen YL, Lau WK, Zhang FX, Fawcett JW, Chan YS, Shum DKY Chondroitin sulfates in the developing rat hindbrain confine commissural projections of vestibular nuclear neurons Neural Development 7 -, 2012
DOI:10.1186/1749-8104-7-6
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Afshari FT, Kwok JC, Fawcett JW Analysis of Schwann-astrocyte interactions using in vitro assays. Journal of visualized experiments : JoVE -, 2011
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Kwok JCF, Dick G, Wang D, Fawcett JW Extracellular matrix and perineuronal nets in CNS repair Developmental Neurobiology 71 1073-1089, 2011
DOI:10.1002/dneu.20974
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Warren P, Kwok J, Smith M, Muir E, Rogers J, Keynes R, Fawcett J MAMMALIAN CHONDROITINASE ABC ENCOURAGES SCHWANN CELL INTEGRATION WITHIN INHIBITORY ENVIRONMENTS GLIA 59 S43-S43, 2011

Zhao RR, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, Roet KCD, Verhaagen J, Schneider BL, Bensadoun JC, Ahmed SG, Yáñez-Muñoz RJ, Keynes RJ, Fawcett JW, Rogers JH Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons Journal of Neuroscience Methods 201 228-238, 2011
DOI:10.1016/j.jneumeth.2011.08.003
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Heller J, Kwok JCF, Martin KR, Fawcett JW Integrin activation increases RPE adhesion to Bruch's membrane components and overcomes tenascin-mediated failure of adhesion in the rat, 2011

Lau NKC, Kwok JCF, Fawcett JW, Lakatos A THROMBOSPONDIN-1 (TSP-1), A SYNAPTOGENIC MOLECULE, IS RE-EXPRESSED IN ADULT GREY MATTER ASTROCYTES AND IN NEURONS RESPONDING TO REMOTE AXONAL INSULTS, 2011

Lin R, Rosahl TW, Whiting PJ, Fawcett JW, Kwok JCF 6-Sulphated chondroitins have a positive influence on axonal regeneration PLoS ONE 6 -, 2011
DOI:10.1371/journal.pone.0021499
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Tan CL, Kwok JCF, Patani R, Ffrench-Constant C, Chandran S, Fawcett JW Integrin activation promotes axon growth on inhibitory chondroitin sulfate proteoglycans by enhancing integrin signaling Journal of Neuroscience 31 6289-6295, 2011
DOI:10.1523/JNEUROSCI.0008-11.2011
View abstract

Afshari FT, Kwok JC, Fawcett JW Analysis of Schwann-astrocyte interactions using in vitro assays Journal of Visualized Experiments -, 2011
DOI:10.3791/2214
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Kwok JCF, Tan CL, Wang D, Heller J, Fawcett JW Chondroitin sulfates in axon regeneration and plasticity Trends in Glycoscience and Glycotechnology 23 201-211, 2011
DOI:10.4052/tigg.23.201
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Hyatt AJT, Wang D, Kwok JC, Fawcett JW, Martin KR Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord Journal of Controlled Release 147 24-29, 2010
DOI:10.1016/j.jconrel.2010.06.026
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Kwok JCF, Carulli D, Fawcett JW In vitro modeling of perineuronal nets: Hyaluronan synthase and link protein are necessary for their formation and integrity Journal of Neurochemistry 114 1447-1459, 2010
DOI:10.1111/j.1471-4159.2010.06878.x
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Carulli D, Pizzorusso T, Kwok JCF, Putignano E, Poli A, Forostyak S, Andrews MR, Deepa SS, Glant TT, Fawcett JW Animals lacking link protein have attenuated perineuronal nets and persistent plasticity Brain 133 2331-2347, 2010
DOI:10.1093/brain/awq145
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Afshari FT, Kwok JC, White L, Fawcett JW Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan GLIA 58 857-869, 2010
DOI:10.1002/glia.20970
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Afshari FT, Kwok JC, Fawcett JW Astrocyte-produced ephrins inhibit Schwann cell migration via VAV2 signaling Journal of Neuroscience 30 4246-4255, 2010
DOI:10.1523/JNEUROSCI.3351-09.2010
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Afshari FT, Kwok JC, Andrews MR, Blits B, Martin KR, Faissner A, Ffrench-Constant C, Fawcett JW Integrin activation or alpha9 expression allows retinal pigmented epithelial cell adhesion on Bruch's membrane in wet age-related macular degeneration Brain 133 448-464, 2010
DOI:10.1093/brain/awp319
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Kwok JC, Carulli D, Fawcett JW IN VITRO MODELING OF PERINEURONAL NET: THE ROLE OF CARTILAGE LINK PROTEIN 1 AND HYALURONAN SYNTHASE IN ITS FORMATION AND INTEGRITY JOURNAL OF NEUROCHEMISTRY 110 37-37, 2009

Gervasi NM, Kwok JCF, Fawcett JW Role of extracellular factors in axon regeneration in the CNS: Implications for therapy Regenerative Medicine 3 907-923, 2008
DOI:10.2217/17460751.3.6.907
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Kwok JCF, Afshari F, García-Alías G, Fawcett JW Proteoglycans in the central nervous system: Plasticity, regeneration and their stimulation with chondroitinase ABC Restorative Neurology and Neuroscience 26 131-145, 2008
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Galtrey CM, Kwok JCF, Carulli D, Rhodes KE, Fawcett JW Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord European Journal of Neuroscience 27 1373-1390, 2008
DOI:10.1111/j.1460-9568.2008.06108.x
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Properzi F, Lin R, Kwok J, Naidu M, Van Kuppevelt TH, Ten Dam GB, Camargo LM, Raha-Chowdhury R, Furukawa Y, Mikami T, Sugahara K, Fawcett JW Heparan sulphate proteoglycans in glia and in the normal and injured CNS: Expression of sulphotransferases and changes in sulphation European Journal of Neuroscience 27 593-604, 2008
DOI:10.1111/j.1460-9568.2008.06042.x
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Lin R, Kwok JCF, Crespo D, Fawcett JW Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain Journal of Neurochemistry 104 400-408, 2008
DOI:10.1111/j.1471-4159.2007.05066.x
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Kwok JCF, Afshari F, Garcia-Alias G, Fawcett J Proteoglycans in the central nervous system: Plasticity, regeneration and their stimulation with chondroitinase ABC RESTORATIVE NEUROLOGY AND NEUROSCIENCE 26 131-145, 2008

Kwok JCF, Vecino E The EXTRACELLULAR MATRIX in the NERVOUS SYSTEM: the GOOD and the BAD ASPECTS In Extracellular Matrix ,
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