Russell Matthews, PhD
RESEARCH PROGRAMS AND AFFILIATIONS
The neural microenvironment in the central nervous system plays critical roles in all stages of development and in proper functioning of the adult nervous system. Alteration or disruption of this neural microenvironment can has profound functional consequences and is implicated in a vast array of neural pathologies and in neural injury. Research in the Matthews laboratory is focused on identifying the cell-surface glycoconjugates and extracellular matrix molecules that are the key organizers in the neural microenvironment. Our work focuses on understanding their roles in the developing nervous system and in neural pathologies and neural trauma. Work from my lab has uncovered the roles of a family of glycoproteins in the establishment and maintenance of the precise connectivity in the central nervous system and we continue to work towards understanding the functional roles of these molecules in learning and memory. Importantly our work has showed that both the proteins themselves and their attached carbohydrates play key roles in brain plasticity and in disorders such as the brain abnormalities in congenital muscular dystrophies. In addition, our work has demonstrated that some of the same molecules and glycosylation pathways are altered in malignant brain tumors (gliomas) and play an important roles in the progression of these diseases. The overarching goal of the work in my laboratory is to identify the molecular substrates of development and disease within the neural microenvironment of the mammalian CNS.
Figure 1 An extracellular matrix structure termed a perineuronal net on a cortical interneuron stained with wisteria floribunda lectin (WFA) in green and GABA A receptor antibody in red.
Figure 2 Cell-specific glycosylation of RPTPz/Phosphacan in neurons and glia. These glycoforms are disrupted in forms of congenital muscular dystrophies with brain abnormalities. Modified from Dwyer at al., 2015.
Figure 3 Specific targeting of an neural microenvironment for glioma therapy. The brevican expressing glioma cell (red) is specifically targeted by nanoparticles (green).
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.Neurobiol Aging. 2017 Nov;59:197-209. doi: 10.1016/j.neurobiolaging.2017.08.002. Epub 2017 Aug 9.PMID:28890301
Blosa M, Bursch C, Weigel S, Holzer M, Jäger C, Janke C, Matthews RT, Arendt T, Morawski M. Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice. Neural Plast. 2016;2016:2828536. doi: 10.1155/2016/2828536. Epub 2015 Dec 27.PMID:26819763
Blosa M, Sonntag M, Jäger C, Weigel S, Seeger J, Frischknecht R, Seidenbecher CI, Matthews RT, Arendt T, Rübsamen R, Morawski M. The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held. J Physiol. 2015 Oct 1;593(19):4341-60. doi: 10.1113/JP270849. Epub 2015 Aug 30.PMID:26223835
Dwyer CA, Katoh T, Tiemeyer M, Matthews RT. Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. J Biol Chem. 2015 Apr 17;290(16):10256-73. doi: 10.1074/jbc.M114.614099. Epub 2015 Mar 3.PMID:25737452
Kind PC, Sengpiel F, Beaver CJ, Crocker-Buque A, Kelly GM, Matthews RT, Mitchell DE. The development and activity-dependent expression of aggrecan in the cat visual cortex. Cereb Cortex. 2013 Feb;23(2):349-60. doi: 10.1093/cercor/bhs015. Epub 2012 Feb 23.PMID:22368089
Jäger C, Lendvai D, Seeger G, Brückner G, Matthews RT, Arendt T, Alpár A, Morawski M. Perineuronal and perisynaptic extracellular matrix in the human spinal cord. Neuroscience. 2013 May 15;238:168-84. doi: 10.1016/j.neuroscience.2013.02.014. Epub 2013 Feb 18.PMID:23428622
Blosa M, Sonntag M, Brückner G, Jäger C, Seeger G, Matthews RT, Rübsamen R, Arendt T, Morawski M. Unique features of extracellular matrix in the mouse medial nucleus of trapezoid body--implications for physiological functions. Neuroscience. 2013 Jan 3;228:215-34. doi: 10.1016/j.neuroscience.2012.10.003. Epub 2012 Oct 13.PMID:23069754
Dwyer CA, Baker E, Hu H, Matthews RT. RPTPζ/phosphacan is abnormally glycosylated in a model of muscle-eye-brain disease lacking functional POMGnT1. Neuroscience. 2012 Sep 18;220:47-61. doi: 10.1016/j.neuroscience.2012.06.026. Epub 2012 Jun 19.PMID:22728091
Giamanco KA, Matthews RT. Deconstructing the perineuronal net: cellular contributions and molecular composition of the neuronal extracellular matrix. Neuroscience. 2012 Aug 30;218:367-84. doi: 10.1016/j.neuroscience.2012.05.055. Epub 2012 May 29.PMID:22659016
Lee JK, Matthews RT, Lim JM, Swanier K, Wells L, Pierce JM. Developmental expression of the neuron-specific N-acetylglucosaminyltransferase Vb (GnT-Vb/IX) and identification of its in vivo glycan products in comparison with those of its paralog, GnT-V. J Biol Chem. 2012 Aug 17;287(34):28526-36. doi: 10.1074/jbc.M112.367565. Epub 2012 Jun 19.PMID:22715095
Morawski M, Brückner G, Jäger C, Seeger G, Matthews RT, Arendt T. Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology. Brain Pathol. 2012 Jul;22(4):547-61. doi: 10.1111/j.1750-3639.2011.00557.x. Epub 2012 Jan 13.PMID:22126211