罗素·马修斯博士

研究抽象

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. 研究 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. 除了, 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. 修改自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).

选定的出版物

Yang S, Hilton S, Alves JN, Saksida LM, Bussey T, 马修斯RT, Kitagawa H, Spillantini MG, Kwok JCF, Fawcett JW.Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration.一般人衰老. 2017年11月,59:197 - 209. doi: 10.1016/j.neurobiolaging.2017.08.002. Epub 2017 8月9日.PMID: 28890301

Blosa M, Bursch C, Weigel S, Holzer M, Jäger C, Janke C, 马修斯RT，阿伦特T，莫拉斯基M. Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice. 神经体. 2016;2016:2828536. doi: 10.1155/2016/2828536. Epub 2015年12月27日.PMID: 26819763

Blosa M, Sonntag M, Jäger C, Weigel S, Seeger J, Frischknecht R, Seidenbecher CI, 马修斯RT，阿伦特T, r bsamen R, Morawski M. The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held. 杂志. 2015年10月1日;593(19):4341-60. doi: 10.1113/JP270849. Epub 2015 8月30日.PMID: 26223835

Dwyer CA, Katoh T, Tiemeyer M， 马修斯RT. Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. 生物化学. 2015年4月17日;290(16):10256-73. doi: 10.1074 / jbc.M114.614099. Epub 2015年3月3日.PMID: 25737452

Kind PC, Sengpiel F, Beaver CJ, Crocker-Buque A, Kelly GM, 马修斯RT米切尔·德. The development and activity-dependent expression of aggrecan in the cat visual cortex. Cereb皮层. 2013年2月,23 (2):349 - 60. doi: 10.1093 / cercor / bhs015. Epub 2012年2月23日.PMID: 22368089

Jäger C, Lendvai D, Seeger G, Brückner G, 马修斯RT，阿伦特T, Alpár A，莫拉斯基M. Perineuronal and perisynaptic extracellular matrix in the human spinal cord. 神经科学. 2013年5月15日;38:168-84. doi: 10.1016/j.神经科学.2013.02.014. Epub 2013年2月18日.PMID: 23428622

Blosa M, Sonntag M, Brückner G, Jäger C, Seeger G, 马修斯RT， r bsamen R，阿伦特T，莫拉斯基M. Unique features of extracellular matrix in the mouse medial nucleus of trapezoid body--implications for physiological functions. 神经科学. 2013年1月3日;28:215-34. doi: 10.1016/j.神经科学.2012.10.003. 2012年10月13日.PMID: 23069754

Dwyer CA, Baker E, Hu H， 马修斯RT. RPTPζ/phosphacan is abnormally glycosylated in a model of muscle-eye-brain disease lacking functional POMGnT1. 神经科学. 2012年9月18日;220:47-61. doi: 10.1016/j.神经科学.2012.06.026. 2012年6月19日.PMID: 22728091

Giamanco KA, 马修斯RT. Deconstructing the perineuronal net: cellular contributions and molecular composition of the neuronal extracellular matrix. 神经科学. 2012年8月30日;218:367-84. doi: 10.1016/j.神经科学.2012.05.055. 2012年5月29日.PMID: 22659016

李JK, 马修斯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. 生物化学. 2012年8月17日;287(34):28526-36. doi: 10.1074 / jbc.M112.367565. 2012年6月19日.PMID: 22715095

Morawski M, Brückner G, Jäger C, Seeger G, 马修斯RT阿伦特·T. Involvement of perineuronal and perisynaptic extracellular matrix in Alzheimer's disease neuropathology. 大脑病理学研究. 2012年7月,22 (4):547 - 61. doi: 10.1111/j.1750-3639.2011.00557.x. 2012年1月13日.PMID: 22126211