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Milner, Richard
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Milner, Richard

Faculty Member Adjunct
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Positions

  • 2018 - Professor Adjunct, Molecular Medicine , Scripps Research
  • 2017 - 2018 Associate Professor of Molecular Medicine, Molecular Medicine , Scripps Research
  • 2004 - 2018 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2012 - 2017 Associate Professor, Molecular and Experimental Medicine (MEM) , Scripps Research
  • 2004 - 2012 Assistant Professor, Molecular and Experimental Medicine (MEM) , Scripps Research
Dr. Richard Milner uses a combination of mouse models and tissue culture cell–based assays to examine the role of fibronectin and endothelial fibronectin receptors in promoting cerebral angiogenesis during cerebral hypoxia and ischemia.

Contact

  • rmilner@scripps.edu

Websites

  • Richard Milner, M.D., Ph.D.
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Publications

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    • Halder, S. K., Milner, R. Chronic mild hypoxia accelerates recovery from preexisting EAE by enhancing vascular integrity and apoptosis of infiltrated monocytes Proceedings of the National Academy of Sciences of the United States of America  2020 117:11126-11135  DOI:10.1073/pnas.1920935117  PMID:32371484  PMCID:PMC7245138
    • Kant, R., Halder, S. K., Fernandez, J. A., Griffin, J. H., Milner, R. Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis Progression by Enhancing Vascular Integrity and Suppressing Microglial Activation Frontiers in Neuroscience  2020 14  DOI:10.3389/fnins.2020.00333  PMID:32351356  PMCID:PMC7174764
    • Halder, S. K., Milner, R. A critical role for microglia in maintaining vascular integrity in the hypoxic spinal cord Proceedings of the National Academy of Sciences of the United States of America  2019 116:26029-26037  DOI:10.1073/pnas.1912178116  PMID:31772011  PMCID:PMC6925983
    • Kant, R., Halder, S. K., Bix, G. J., Milner, R. Absence of endothelial α5β1 integrin triggers early onset of experimental autoimmune encephalomyelitis due to reduced vascular remodeling and compromised vascular integrity Acta Neuropathologica Communications  2019 7  DOI:10.1186/s40478-019-0659-9  PMID:30678721  PMCID:PMC6346510
    • Halder, S. K., Kant, R., Milner, R. Chronic mild hypoxia increases expression of laminins 111 and 411 and the laminin receptor α6β1 integrin at the blood-brain barrier Brain Research  2018 1700:78-85  DOI:10.1016/j.brainres.2018.07.012  PMID:30006296  PMCID:PMC6231956
    • Pang, D., Wang, L., Dong, J., Lai, X., Huang, Q., Milner, R., Li, L. Integrin α5β1-Ang1/Tie2 receptor cross-talk regulates brain endothelial cell responses following cerebral ischemia Experimental and Molecular Medicine  2018 50  DOI:10.1038/s12276-018-0145-7
    • Halder, S. K., Kant, R., Milner, R. Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels Acta Neuropathologica Communications  2018 6  DOI:10.1186/s40478-018-0590-5  PMID:30176931  PMCID:PMC6122733
    • Halder, S. K., Kant, R., Milner, R. Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism Angiogenesis  2018 21:251-266  DOI:10.1007/s10456-017-9593-2  PMID:29299782
    • Welser, J. V., Halder, S. K., Kant, R., Boroujerdi, A., Milner, R. Endothelial α6β4 integrin protects during experimental autoimmune encephalomyelitis-induced neuroinflammation by maintaining vascular integrity and tight junction protein expression Journal of Neuroinflammation  2017 14  DOI:10.1186/s12974-017-0987-2  PMID:29121970  PMCID:PMC5679365
    • Sun, J., Yu, L., Huang, S., Lai, X., Milner, R., Li, L. Vascular expression of angiopoietin1, α5β1 integrin and tight junction proteins is tightly regulated during vascular remodeling in the post-ischemic brain Neuroscience  2017 362:248-256  DOI:10.1016/j.neuroscience.2017.08.040  PMID:28864200
    • Burnier, L., Boroujerdi, A., Fernandez, J. A., Welser-Alves, J. V., Griffin, J. H., Milner, R. Physiological cerebrovascular remodeling in response to chronic mild hypoxia: A role for activated protein C Experimental Neurology  2016 283:396-403  DOI:10.1016/j.expneurol.2016.07.004  PMID:27412766  PMCID:PMC4992591
    • Johnson, K. M., Milner, R., Crocker, S. J. Extracellular matrix composition determines astrocyte responses to mechanical and inflammatory stimuli Neuroscience Letters  2015 600:104-109  DOI:10.1016/j.neulet.2015.06.013  PMID:26067407  PMCID:PMC4530625
    • Boroujerdi, A., Welser-Alves, J. V., Milner, R. Matrix metalloproteinase-9 mediates post-hypoxic vascular pruning of cerebral blood vessels by degrading laminin and claudin-5 Angiogenesis  2015 18:255-264  DOI:10.1007/s10456-015-9464-7  PMID:25812799
    • Boroujerdi, A., Milner, R. Defining the critical hypoxic threshold that promotes vascular remodeling in the brain Experimental Neurology  2015 263:132-140  DOI:10.1016/j.expneurol.2014.10.007  PMID:25448157  PMCID:PMC4261640
    • Huang, Q., Chen, B., Wang, F., Huang, H., Milner, R., Li, L. The temporal expression patterns of fibronectin and its receptors-α5β1 and αvβ3 integrins on blood vessels after cerebral ischemia Restorative Neurology and Neuroscience  2015 33:493-507  DOI:10.3233/rnn-140491  PMID:26409408
    • Welser-Alves, J. V., Boroujerdi, A., Tigges, U., Milner, R. Analysis of TNF-alpha-mediated cerebral pericyte remodeling Methods in Molecular Biology  2014 1155:81-93  DOI:10.1007/978-1-4939-0669-7_8  PMID:24788175
    • Boroujerdi, A., Welser-Alves, J. V., Milner, R. Examining vascular remodeling in the hypoxic central nervous system Methods in Molecular Biology  2014 1135:177-186  DOI:10.1007/978-1-4939-0320-7_15  PMID:24510864
    • Welser-Alves, J. V., Boroujerdi, A., Milner, R. Isolation and culture of primary mouse brain endothelial cells Methods in Molecular Biology  2014 1135:345-356  DOI:10.1007/978-1-4939-0320-7_28  PMID:24510877
    • Boroujerdi, A., Tigges, U., Welser-Alves, J. V., Milner, R. Isolation and culture of primary pericytes from mouse brain Methods in Molecular Biology  2014 1135:383-392  DOI:10.1007/978-1-4939-0320-7_31  PMID:24510880
    • Boroujerdi, A., Welser-Alves, J. V., Milner, R. Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the alpha 5 beta 1 integrin Experimental Neurology  2013 250:43-51  DOI:10.1016/j.expneurol.2013.09.009  PMID:24056042  PMCID:PMC4235607
    • Welser-Alves, J. V., Milner, R. Microglia are the major source of TNF-α and TGF-β1 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin Neurochemistry International  2013 63:47-53  DOI:10.1016/j.neuint.2013.04.007  PMID:23619393  PMCID:PMC3819935
    • Welser-Alves, J. V., Boroujerdi, A., Tigges, U., Wrabetz, L., Feltri, M. L., Milner, R. Endothelial beta4 integrin is predominantly expressed in arterioles, where it promotes vascular remodeling in the hypoxic brain Arteriosclerosis, Thrombosis, and Vascular Biology  2013 33:943-953  DOI:10.1161/atvbaha.112.300566  PMID:23471230
    • Tigges, U., Boroujerdi, A., Welser-Alves, J. V., Milner, R. TNF-alpha promotes cerebral pericyte remodeling in vitro, via a switch from alpha1 to alpha2 integrins Journal of Neuroinflammation  2013 10:33  DOI:10.1186/1742-2094-10-33  PMID:23448258  PMCID:PMC3616978
    • Li, L. X., Welser-Alves, J., van der Flier, A., Boroujerdi, A., Hynes, R. O., Milner, R. An angiogenic role for the alpha 5 beta 1 integrin in promoting endothelial cell proliferation during cerebral hypoxia Experimental Neurology  2012 237:46-54  DOI:10.1016/j.expneurol.2012.06.005  PMID:22721769  PMCID:PMC3748139
    • Boroujerdi, A., Welser-Alves, J. V., Tigges, U., Milner, R. Chronic cerebral hypoxia promotes arteriogenic remodeling events that can be identified by reduced endoglin (CD105) expression and a switch in beta 1 integrins Journal of Cerebral Blood Flow and Metabolism  2012 32:1820-1830  DOI:10.1038/jcbfm.2012.94  PMID:22739620  PMCID:PMC3434638
    • Tigges, U., Welser-Alves, J. V., Boroujerdi, A., Milner, R. A novel and simple method for culturing pericytes from mouse brain Microvascular Research  2012 84:74-80  DOI:10.1016/j.mvr.2012.03.008  PMID:22484453  PMCID:PMC3748138
    • del Zoppo, G. J., Frankowski, H., Gu, Y. H., Osada, T., Kanazawa, M., Milner, R., Wang, X. Y., Hosomi, N., Mabuchi, T., Koziol, J. A. Microglial cell activation is a source of metalloproteinase generation during hemorrhagic transformation Journal of Cerebral Blood Flow and Metabolism  2012 32:919-932  DOI:10.1038/jcbfm.2012.11  PMID:22354151  PMCID:PMC3345906
    • Welser, J. V., Milner, R. Derivation of microglia-free astrocyte cultures from neural stem cells Methods in Molecular Biology  2012 814:81-91  DOI:10.1007/978-1-61779-452-0_6  PMID:22144301
    • Li, L. X., Liu, F. D., Welser-Alves, J. V., McCullough, L. D., Milner, R. Upregulation of fibronectin and the α5β1 and αvβ3 integrins on blood vessels within the cerebral ischemic penumbra Experimental Neurology  2012 233:283-291  DOI:10.1016/j.expneurol.2011.10.017  PMID:22056225  PMCID:PMC3748136
    • Welser, J. V., Milner, R. Use of astrocyte-microglial cocultures to examine the regulatory influence of astrocytes on microglial activation Methods in Molecular Biology  2012 814:367-380  DOI:10.1007/978-1-61779-452-0_24  PMID:22144319
    • Frankowski, H., Gu, Y. H., Heo, J. H., Milner, R., Del Zoppo, G. J. Use of gel zymography to examine matrix metalloproteinase (gelatinase) expression in brain tissue or in primary glial cultures Methods in Molecular Biology  2012 814:221-233  DOI:10.1007/978-1-61779-452-0_15  PMID:22144310  PMCID:PMC3670093
    • Welser-Alves, J. V., Boroujerdi, A., Tigges, U., Milner, R. Microglia use multiple mechanisms to mediate interactions with vitronectin; non-essential roles for the highly-expressed alpha v beta 3 and alpha v beta 5 integrins Journal of Neuroinflammation  2011 8:157  DOI:10.1186/1742-2094-8-157  PMID:22074485  PMCID:PMC3239846
    • Osada, T., Gu, Y. H., Kanazawa, M., Tsubota, Y., Hawkins, B. T., Spatz, M., Milner, R., del Zoppo, G. J. Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins Journal of Cerebral Blood Flow and Metabolism  2011 31:1972-1985  DOI:10.1038/jcbfm.2011.99  PMID:21772312  PMCID:PMC3208159
    • Welser-Alves, J. V., Crocker, S. J., Milner, R. A dual role for microglia in promoting tissue inhibitor of metalloproteinase (timp) expression in glial cells in response to neuroinflammatory stimuli Journal of Neuroinflammation  2011 8:61  DOI:10.1186/1742-2094-8-61  PMID:21631912  PMCID:PMC3120696
    • Tsueng, G., Tabor-Godwin, J. M., Gopal, A., Ruller, C. M., Deline, S., An, N., Frausto, R. F., Milner, R., Crocker, S. J., Whitton, J. L., Feuer, R. Coxsackievirus preferentially replicates and induces cytopathic effects in undifferentiated neural progenitor cells Journal of Virology  2011 85:5718-5732  DOI:10.1128/jvi.02261-10  PMID:21471247  PMCID:PMC3126326
    • Moore, C. S., Milner, R., Nishiyama, A., Frausto, R. F., Serwanski, D. R., Pagarigan, R. R., Whitton, J. L., Miller, R. H., Crocker, S. J. Astrocytic tissue inhibitor of metalloproteinase-1 (timp-1) promotes oligodendrocyte differentiation and enhances cns myelination Journal of Neuroscience  2011 31:6247-6254  DOI:10.1523/jneurosci.5474-10.2011  PMID:21508247  PMCID:PMC3090636
    • Welser, J. V., Li, L. X., Milner, R. Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of tnf and tgf-beta 1 Journal of Neuroinflammation  2010 7:89  DOI:10.1186/1742-2094-7-89  PMID:21134289  PMCID:PMC3016272
    • Pian, J. P., Criado, J. R., Milner, R., Ehlers, C. L. N-methyl-D-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure Neuroscience  2010 170:645-654  DOI:10.1016/j.neuroscience.2010.06.065  PMID:20603193  PMCID:PMC2945397
    • Li, L. X., Welser, J. V., Dore-Duffy, P., Del Zoppo, G. J., Lamanna, J. C., Milner, R. In the hypoxic central nervous system, endothelial cell proliferation is followed by astrocyte activation, proliferation, and increased expression of the alpha 6 beta 4 integrin and dystroglycan Glia  2010 58:1157-1167  DOI:10.1002/glia.20995  PMID:20544851  PMCID:PMC2914614
    • Li, L. X., Welser, J. V., Milner, R. Absence of the alpha v beta 3 integrin dictates the time-course of angiogenesis in the hypoxic central nervous system: Accelerated endothelial proliferation correlates with compensatory increases in alpha 5 beta 1 integrin expression Journal of Cerebral Blood Flow and Metabolism  2010 30:1031-1043  DOI:10.1038/jcbfm.2009.276  PMID:20087368  PMCID:PMC2949180
    • Milner, R. Microglial expression of alpha v beta 3 and alpha v beta 5 integrins is regulated by cytokines and the extracellular matrix: Beta 5 integrin null microglia show no defects in adhesion or mmp-9 expression on vitronectin Glia  2009 57:714-723  DOI:10.1002/glia.20799  PMID:18985734
    • Crocker, S. J., Frausto, R. F., Whitton, J. L., Milner, R. A novel method to establish microglia-free astrocyte cultures: Comparison of matrix metalloproteinase expression profiles in pure cultures of astrocytes and microglia Glia  2008 56:1187-1198  DOI:10.1002/glia.20689  PMID:18449943  PMCID:PMC2776034
    • Milner, R., Hung, S., Erokwu, B., Dore-Duffy, P., LaManna, J. C., del Zoppo, G. J. Increased expression of fibronectin and the alpha 5 beta 1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia Molecular and Cellular Neuroscience  2008 38:43-52  DOI:10.1016/j.mcn.2008.01.013  PMID:18343155  PMCID:PMC2588547
    • Milner, R., Hung, S., Wang, X., Spatz, M., del Zoppo, G. J. The rapid decrease in astrocyte-associated dystroglycan expression by focal cerebral ischemia is protease-dependent Journal of Cerebral Blood Flow and Metabolism  2008 28:812-823  DOI:10.1038/sj.jcbfm.9600585  PMID:18030304  PMCID:PMC2588545
    • Milner, R., Hung, S., Wang, X., Berg, G. I., Spatz, M., del Zoppo, G. J. Responses of endothelial cell and astrocyte matrix-integrin receptors to ischemia mimic those observed in the neurovascular unit Stroke  2008 39:191-197  DOI:10.1161/strokeaha.107.486134  PMID:18032737  PMCID:PMC2588548
    • Crocker, S. J., Frausto, R. F., Whitmire, J. K., Benning, N., Milner, R., Whitton, J. L. Amelioration of coxsackievirus b3-mediated myocarditis by inhibition of tissue inhibitors of matrix metalloproteinase-1 American Journal of Pathology  2007 171:1762-1773  DOI:10.2353/ajpath.2007.070179  PMID:18055551  PMCID:PMC2111101
    • Milner, R., Crocker, S. J., Hung, S., Wang, X. Y., Frausto, R. F., del Zoppo, G. J. Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins alpha(5)beta(1) and alpha(v)beta(5) Journal of Immunology  2007 178:8158-8167  PMID:17548654
    • del Zoppo, G. J., Milner, R., Mabuchi, T., Hung, S., Wang, X. Y., Berg, G. I., Koziol, J. A. Microglial activation and matrix protease generation during focal cerebral ischemia Stroke  2007 38:646-651  DOI:10.1161/01.STR.0000254477.34231.cb  PMID:17261708
    • Milner, R. A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous system BMC Neuroscience  2007 8:3  DOI:10.1186/1471-2202-8-3  PMID:17199896  PMCID:PMC1769506
    • Milner, R., Campbell, I. L. Increased expression of the beta 4 and alpha 5 integrin subunits in cerebral blood vessels of transgenic mice chronically producing the pro-inflammatory cytokines il-6 or ifn-alpha, in the central nervous system Molecular and Cellular Neuroscience  2006 33:429-440  DOI:10.1016/j.mcn.2006.09.004  PMID:17049262  PMCID:PMC1847624
    • del Zoppo, G. J., Milner, R., Mabuchi, T., Hung, S., Wang, X., Koziol, J. A. Vascular matrix adhesion and the blood-brain barrier Biochemical Society Transactions  2006 34:1261-1266  PMID:17073798
    • del Zoppo, G. J., Milner, R. Integrin-matrix interactions in the cerebral microvasculature Arteriosclerosis, Thrombosis, and Vascular Biology  2006 26:1966-1975  DOI:10.1161/01.ATV.0000232525.65682.a2  PMID:16778120
    • Crocker, S. J., Milner, R., Pham-Mitchell, N., Campbell, I. L. Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells Journal of Neurochemistry  2006 98:812-823  DOI:10.1111/j.1471-4159.2006.03927.x  PMID:16893421
    • Wang, J., Milner, R. Fibronectin promotes brain capillary endothelial cell survival and proliferation through alpha 5 beta 1 and alpha v beta 3 integrins via map kinase signalling Journal of Neurochemistry  2006 96:148-159  DOI:10.1111/j.1471-4159.2005.03521.x  PMID:16269008
    • Milner, R., Campbell, I. L. The extracellular matrix and cytokines regulate microglial integrin expression and activation Journal of Immunology  2003 170:3850-3858  PMID:12646653
    • Milner, R., Campbell, I. L. Developmental regulation of beta 1 integrins during angiogenesis in the central nervous system Molecular and Cellular Neuroscience  2002 20:616-626  DOI:10.1006/mcne.2002.1151  PMID:12213443
    • Milner, R., Campbell, I. L. The integrin family of cell adhesion molecules has multiple functions within the cns Journal of Neuroscience Research  2002 69:286-291  DOI:10.1002/jnr.10321  PMID:12125070
    • Milner, R., Campbell, I. L. Cytokines regulate microglial adhesion to laminin and astrocyte extracellular matrix via protein kinase c-dependent activation of the alpha 6 beta 1 integrin Journal of Neuroscience  2002 22:1562-1572  PMID:11880486
    • Asensio, V. C., Maier, J., Milner, R., Boztug, K., Kincaid, C., Moulard, M., Phillipson, C., Lindsley, K., Krucker, T., Fox, H. S., Campbell, I. L. Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of cxcl10/ip-10 gene expression by astrocytes in vivo and in vitro Journal of Virology  2001 75:7067-7077  DOI:10.1128/jvi.75.15.7067-7077.2001  PMID:11435587
    • Milner, R., Relvas, J. I. B., Fawcett, J., ffrench-Constant, C. Developmental regulation of alpha v integrins produces functional changes in astrocyte behavior Molecular and Cellular Neuroscience  2001 18:108-118  DOI:10.1006/mcne.2001.1003  PMID:11461157
    • Frost, E. E., Milner, R., Ffrench-Constant, C. Migration assays for oligodendrocyte precursor cells Methods in Molecular Biology  2000 139:265-278  DOI:10.1385/1-59259-063-2:265  PMID:10840794
    • Milner, R., Huang, X. Z., Wu, J. F., Nishimura, S., Pytela, R., Sheppard, D., ffrench-Constant, C. Distinct roles for astrocyte alpha v beta 5 and alpha v beta 8 integrins in adhesion and migration Journal of Cell Science  1999 112:4271-4279  PMID:10564645
    • Frost, E. E., Buttery, P. C., Milner, R., ffrench-Constant, C. Integrins mediate a neuronal survival signal for oligodendrocytes Current Biology  1999 9:1251-1254  DOI:10.1016/s0960-9822(99)80506-5  PMID:10556090
    • Buttery, P. C., Mallawaarachchi, C. M., Milner, R., Doherty, P., ffrench-Constant, C. Mapping regions of the beta 1 integrin cytoplasmic domain involved in migration and survival in primary oligodendrocyte precursors using cell-permeable homeopeptides Biochemical and Biophysical Research Communications  1999 259:121-127  DOI:10.1006/bbrc.1999.0726  PMID:10334926
    • Oldroyd, B., Truscott, J. G., Woodrow, G., Milner, R., Stewart, S. P., Smith, A. H., Westmacott, C. F., Smith, M. A. Comparison of in vivo body composition using two Lunar dual-energy X-ray absorptiometers European Journal of Clinical Nutrition  1998 52:180-185  DOI:10.1038/sj.ejcn.1600537  PMID:9537303
    • Milner, R., Frost, E., Nishimura, S., Delcommenne, M., Streuli, C., Pytela, R., FfrenchConstant, C. Expression of alpha v beta 3 and alpha v beta 8 integrins during oligodendrocyte precursor differentiation in the presence and absence of axons Glia  1997 21:350-360  DOI:10.1002/(sici)1098-1136(199712)21:4<350::aid-glia2>3.3.co;2-g  PMID:9419010
    • Milner, R., Wilby, M., Nishimura, S., Boylen, K., Edwards, G., Fawcett, J., Streuli, C., Pytela, R., ffrenchConstant, C. Division of labor of schwann cell integrins during migration on peripheral nerve extracellular matrix ligands Developmental Biology  1997 185:215-228  DOI:10.1006/dbio.1997.8547  PMID:9187084
    • Jefferson, S., Jacques, T., Kiernan, B. W., ScottDrew, S., Milner, R., ffrenchConstant, C. Inhibition of oligodendrocyte precursor motility by oligodendrocyte processes: Implications for transplantation-based approaches to multiple sclerosis Multiple Sclerosis  1997 3:162-167  PMID:9291174
    • Milner, R. Understanding the molecular basis of cell migration; implications for clinical therapy in multiple sclerosis Clinical Science  1997 92:113-122  PMID:9059311
    • Milner, R., Anderson, H. J., Rippon, R. F., McKay, J. S., Franklin, R. J. M., Marchionni, M. A., Reynolds, R., FfrenchConstant, C. Contrasting effects of mitogenic growth factors on oligodendrocyte precursor cell migration Glia  1997 19:85-90  DOI:10.1002/(sici)1098-1136(199701)19:1<85::aid-glia9>3.0.co;2-9  PMID:8989571
    • Milner, R., Edwards, G., Streuli, C., FfrenchConstant, C. A role in migration for the alpha v beta 1 integrin expressed on oligodendrocyte precursors Journal of Neuroscience  1996 16:7240-7252  PMID:8929432
    • Shaw, C. E., Milner, R., Compston, A. S., ffrenchConstant, C. Analysis of integrin expression on oligodendrocytes during axo-glial interaction by using rat-mouse xenocultures Journal of Neuroscience  1996 16:1163-1172  PMID:8558245
    • Franklin, R. J. M., Bayley, S. A., Milner, R., Ffrenchconstant, C., Blakemore, W. F. Differentiation of the o-2a progenitor-cell line cg-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of cns white-matter Glia  1995 13:39-44  DOI:10.1002/glia.440130105  PMID:7751054
    • Milner, R., Ffrenchconstant, C. A developmental analysis of oligodendroglial integrins in primary-cells - changes in alpha-v-associated beta-subunits during differentiation Development  1994 120:3497-3506  PMID:7821217
    • Ffrenchconstant, C., Kiernan, B. W., Milner, R., Stottdrew, S. Developmental studies of oligodendrocyte precursor cell-migration and their implications for transplantation as therapy for multiple-sclerosis Eye  1994 8:221-223  PMID:7958026
    • Harrison, S., Milner, R., Boyett, M. Influence of Ca2+ channel agonists and antagonists on the post-rest staircase European Journal of Pharmacology  1993 237:83-92  DOI:10.1016/0014-2999(93)90096-z  PMID:7689472
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Research

research overview

  • Regulation of Cerebral Angiogenesis by the Extracellular Matrix

    The goal of our research is to understand how extracellular matrix (ECM) proteins regulate blood vessel growth in the central nervous system (CNS). During development, endothelial cells switch from an angiogenic phenotype into a stable differentiated phenotype, and this coincides with a switch in expression, from fibronectin receptors during angiogenesis, to laminin receptors in the adult. In vitro studies reveal that fibronectin strongly promotes brain endothelial cell survival and proliferation, and that this effect is mediated via the fibronectin receptors, α5β1 and αvβ3 integrins. To examine whether angiogenesis in the adult CNS is also associated with induction of fibronectin and its receptors we examined this process in a mouse model of hypoxia. In the hypoxic CNS, fibronectin and the α5β1 integrin were strongly upregulated on angiogenic vessels, suggesting that the α5β1 integrin may be important in driving angiogenesis in the adult CNS. Currently we are using knockout mice and a combination of in vivo and in vitro approaches to define the roles of the α5β1 and αvβ3 integrins at specific stages of cerebral angiogenesis.

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Background

education and training

  • M.D. in Medicine and Surgery, University of Cambridge , (M.B., B.Chir.) 1998
  • Ph.D. in Developmental Neurobiology, University of Cambridge 1994
  • B.S. in Physiology, University of Leeds 1990
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Contact

full name

  • David Richard Milner

geographic location

  • Scripps California 

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