Prof Christiana Ruhrberg

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Personal Profile

Name: Christiana Ruhrberg Email: c.ruhrberg@ucl.ac.uk
Title: Prof Tel: 020 7608 4017
Department: Inst Ophthalmology - Cell Biology Fax: 020 7608 6810
Position: Professor of Neuronal and Vascular Biology Address: 11-43 Bath Street, , London, EC1V 9EL
Research Domain: Basic Life Sciences, Cardiometabolic Science, Neuroscience, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

Vascular dysfunction and neovascularisation contribute to many diseases. For example, vision loss in two common eye diseases, diabetic retinopathy and age-related macular degeneration. Accordingly, the study of vascular growth is of enormous clinical significance. Both physiological and pathological vascularisation have been studied extensively, and much of this work has highlighted the critical role of the vascular growth factor VEGF and its receptors.

We have previously shown that VEGF isoforms control vascular patterning through their differential distribution in the extracellular matrix. This mechanism ensures that a well-connected vascular network forms in the brain and retina. We are presently examining the role of the extracellular matrix in VEGF isoform distribution and the role of isoform-specific VEGF receptors with the aim of identifying specific mechanisms that may be targeted by therapeutic intervention in neovascular eye disease. We also want to understand how growing blood vessels integrate into the developing brain and retina without disrupting the organisation and function of neurons and glia, and how microglia and macrophages modulate vascular growth. This knowledge will help us to develop clinical strategies aimed at repairing the vascular supply to ischemic eyes.

To learn more about the cross talk of growing vessels with neurons, we are studying signalling pathways implicated in neuronal and vascular growth and patterning. One such candidate signalling pathway uses the transmembrane protein neuropilin 1 (NRP1), a cell surface receptor for two different types of secreted glycoproteins: an isoform of VEGF termed VEGF164 and the repulsive guidance cue SEMA3A. To understand NRP1 function, we are identifying roles for these NRP1 ligands in both blood vessels and nerves. For example, we have shown that VEGF164/NRP1 signalling controls motor neuron migration in the brain stem and retinal axon guidance at the optic chiasm. Moreover, we have found that SEMA3A/NRP1 controls cranial neural crest migration and thereby patterns the peripheral nervous system. Other current projects focus on the development of the sympathetic nervous system and Schwann cell glia.


Research Activities

Neurovascular copatterning

Normal and abnormal development of the neuromuscular components of the gut

Education Description

UCL Collaborators

Dr Vassilis Pachnis; Prof Kristjan Jessen; Prof Rhona Mirsky; Prof Philip Beales; Dr Nikhil Thapar; Dr Alan Burns

External Collaborators

Professor Robert Hofstra; Dr Allan Goldstein; Professor Wood Yee Chan

Publications

    2014

    • Plein A, Fantin A, Ruhrberg C (2014). Neuropilin regulation of angiogenesis, arteriogenesis and vascular permeability.. Microcirculation, , - . doi:10.1111/micc.12124
    • Raimondi C, Fantin A, Lampropoulou A, Denti L, Chikh A, Ruhrberg C (2014). Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.. J Exp Med, , - . doi:10.1084/jem.20132330
    • Tillo M, Schwarz Q, Ruhrberg C (2014). Mouse hindbrain ex vivo culture to study facial branchiomotor neuron migration.. J Vis Exp, (85), - . doi:10.3791/51397
    • Fantin A, Herzog B, Mahmoud M, Yamaji M, Plein A, Denti L, Ruhrberg C, Zachary I (2014). Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis.. Development, , - . doi:10.1242/dev.103028
    • Delalande JM, Vernay B, Natarajan D, Finlay M, Ruhrberg C, Thapar N, Burns AJ (2014). Vascularisation is not necessary for gut colonisation by enteric neural crest cells. Developmental Biology, 385(2), 220 - 229. doi:10.1016/j.ydbio.2013.11.007
    • Zachary I, Fantin A, Herzog B, Mahmoud M, Yamaji M, Plein A, Denti L, Ruhrberg C (2014). P197Neuropilin (NRP) 1 hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis.. Cardiovasc Res, 103 Suppl 1, S35 - . doi:10.1093/cvr/cvu082.132
    • Plein A, Fantin A, Ruhrberg C (2014). Distinguishing cell-type specific roles for NRP1 in the developing heart.

    2013

    • Raimondi C, Ruhrberg C (2013). Neuropilin signalling in vessels, neurons and tumours.. Semin Cell Dev Biol, 24(3), 172 - 178. doi:10.1016/j.semcdb.2013.01.001
    • Fantin A, Vieira JM, Plein A, Denti L, Fruttiger M, Pollard JW, Ruhrberg C (2013). NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis.. Blood, 121(12), 2352 - 2362. doi:10.1182/blood-2012-05-424713
    • Ruhrberg C, Raimondi C, Wall I, Uniewicz K, Fernig D (2013). Defining novels roles for NRP1 in angiogenesis. doi:10.1007/s10456-012-9326-5
    • Fantin A, Vieira JM, Plein A, Maden CH, Ruhrberg C (2013). The embryonic mouse hindbrain as a qualitative and quantitative model for studying the molecular and cellular mechanisms of angiogenesis.. Nat Protoc, 8(2), 418 - 429. doi:10.1038/nprot.2013.015
    • Ruhrberg C, Bautch VL (2013). Neurovascular development and links to disease.. Cell Mol Life Sci, 70(10), 1675 - 1684. doi:10.1007/s00018-013-1277-5
    • Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M (2013). The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis.. Dev Cell, 25(2), 156 - 168. doi:10.1016/j.devcel.2013.03.019
    • Erskine L, Bruce FM, Denti L, Tilo M, Ruhrberg C (2013). Neural-vascular interactions in the control of axon organisation and laterality in the developing visual system.
    • Seerapu HR, Borthakur S, Kong N, Agrawal S, Drazba J, Vasanji A, Fantin A, Ruhrberg C, Buck M, Horowitz A (2013). The cytoplasmic domain of neuropilin-1 regulates focal adhesion turnover.. FEBS Lett, , - . doi:10.1016/j.febslet.2013.08.040

    2012

    • Ruhrberg C (2012). The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications. In Zudaire E, Cuttitta F (Ed.), The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications (pp. - ). : Springer.
    • Maden CH, Gomes J, Schwarz Q, Davidson K, Tinker A, Ruhrberg C (2012). NRP1 and NRP2 cooperate to regulate gangliogenesis, axon guidance and target innervation in the sympathetic nervous system.. Dev Biol, 369(2), 277 - 285. doi:10.1016/j.ydbio.2012.06.026
    • Tillo M, Ruhrberg C, Mackenzie F (2012). Emerging roles for semaphorins and VEGFs in synaptogenesis and synaptic plasticity.. Cell Adh Migr, 6(6), 541 - 546. doi:10.4161/cam.22408
    • Mackenzie F, Ruhrberg C (2012). Diverse roles for VEGF-A in the nervous system.. Development, 139(8), 1371 - 1380. doi:10.1242/dev.072348
    • Bouvrée K, Brunet I, Del Toro R, Gordon E, Prahst C, Cristofaro B, Mathivet T, Xu Y, Soueid J, Fortuna V, Miura N, Aigrot MS, Maden CH, Ruhrberg C, Thomas JL, Eichmann A (2012). Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation.. Circ Res, 111(4), 437 - 445. doi:10.1161/CIRCRESAHA.112.269316

    2011

    • Hernández-Miranda LR, Cariboni A, Faux C, Ruhrberg C, Cho JH, Cloutier JF, Eickholt BJ, Parnavelas JG, Andrews WD (2011). Robo1 regulates semaphorin signaling to guide the migration of cortical interneurons through the ventral forebrain.. J Neurosci, 31(16), 6174 - 6187. doi:10.1523/JNEUROSCI.5464-10.2011
    • Erskine L, Reijntjes S, Pratt T, Denti L, Schwarz Q, Vieira JM, Alakakone B, Shewan D, Ruhrberg C (2011). VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm.. Neuron, 70(5), 951 - 965. doi:10.1016/j.neuron.2011.02.052
    • Wansbury O, Mackay A, Kogata N, Mitsopoulos C, Kendrick H, Davidson K, Ruhrberg C, Reis-Filho JS, Smalley MJ, Zvelebil M, Howard BA (2011). Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment.. Breast Cancer Res, 13(4), R79 - . doi:10.1186/bcr2928
    • Fantin A, Schwarz Q, Davidson K, Normando EM, Denti L, Ruhrberg C (2011). The cytoplasmic domain of neuropilin 1 is dispensable for angiogenesis, but promotes the spatial separation of retinal arteries and veins.. Development, 138(19), 4185 - 4191. doi:10.1242/dev.070037
    • Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, Ruhrberg C, Cantley LG (2011). Distinct macrophage phenotypes contribute to kidney injury and repair.. J Am Soc Nephrol, 22(2), 317 - 326. doi:10.1681/ASN.2009060615
    • Barraud P, Seferiadis AA, Tyson LD, Zwart MF, Szabo-Rogers HL, Ruhrberg C, Liu KJ, Baker CVH (2011). Neural Crest Origin of Olfactory Ensheathing Glia. Proc Natl Acad Sci U S A, in press, - . doi:10.1073/pnas.1012248107
    • Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi B, Ruhrberg C, Cantley LG (2011). Kidney Injury and Repair Utilize Distinct Macrophage Phenotypes. Journal of the American Society of Nephrology, in press, - .
    • Cariboni A, Ruhrberg C (2011). The hormone of love attracts a partner for life.. Dev Cell, 21(4), 602 - 604. doi:10.1016/j.devcel.2011.09.018
    • Fantin A, Schwarz Q, Davidson K, Denti L, Ruhrberg C (2011). The cytoplasmic domain of neuropilin 1 is dispensable for angiogenesis, but imposes spatial separation of retinal arteries and veins.
    • Cariboni A, Davidson K, Dozio E, Memi F, Schwarz Q, Stossi F, Parnavelas JG, Ruhrberg C (2011). VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels.. Development, 138(17), 3723 - 3733. doi:10.1242/dev.063362

    2010

    • Cariboni A, Davidson K, Rakic S, Maggi R, Parnavelas J, Ruhrberg C (2010). Defective GnRH neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for Kallmann Syndrome. Human Molecular Genetics, in press, - . doi:10.1093/hmg/ddq468
    • Ruhrberg C, Schwarz Q (2010). In the beginning: Generating neural crest cell diversity.. Cell Adh Migr, 4(4), 622 - 630. doi:10.4161/cam.4.4.13502
    • Ruhrberg C, De Palma M (2010). A double agent in cancer: deciphering macrophage roles in human tumors.. Nat Med, 16(8), 861 - 862. doi:10.1038/nm0810-861
    • Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C (2010). Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction.. Blood, 116(5), 829 - 840. doi:10.1182/blood-2009-12-257832
    • Vieira JM, Ruhrberg C, Schwarz Q (2010). VEGF receptor signaling in vertebrate development.. Organogenesis, 6(2), 97 - 106.
    • Schwarz Q, Ruhrberg C (2010). Neuropilin, you gotta let me know: should I stay or should I go?. Cell Adh Migr, 4(1), 61 - 66.

    2009

    • Schwarz Q, Vieira JM, Howard B, Eickholt BJ, Ruhrberg C (2009). Neuropilin 1 and 2 control cranial gangliogenesis and axon guidance through neural crest cells (vol 135, pg 1605, 2009). DEVELOPMENT, 136(2), 347 - 347. doi:10.1242/dev.033316
    • Schwarz Q, Maden C, Davidson K, Ruhrberg C (2009). Coordinating neural crest stem cell migration with cell specification. doi:10.1016/j.mod.2009.06.767
    • Schwarz Q, Maden CH, Davidson K, Ruhrberg C (2009). Neuropilin-mediated neural crest cell guidance is essential to organise sensory neurons into segmented dorsal root ganglia. Development, 136(11), 1785 - 1789. doi:10.1242/dev.034322
    • Maden C, Schwarz Q, Ruhrberg C (2009). Neuropilin signalling controls sequential stages of sympathetic development. doi:10.1016/j.mod.2009.06.583
    • Fantin A, Maden CH, Ruhrberg C (2009). Neuropilin ligands in vascular and neuronal patterning.. Biochem Soc Trans, 37(Pt 6), 1228 - 1232. doi:10.1042/BST0371228
    • Schwarz Q, Maden CH, Vieira JM, Ruhrberg C (2009). Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification. Proc.Natl.Acad.Sci.U.S.A, 106(15), 6164 - 6169. doi:10.1073/pnas.0811521106
    • Ruhrberg C, Maden C, Schwarz Q (2009). Neuropilin 1 controls cardiovascular development through neural crest cells. FASEB JOURNAL, 23, - .

    2008

    • Ruhrberg (2008). VEGF in Development.
    • Schwarz Q, Waimey KE, Golding M, Takamatsu H, Kumanogoh A, Fujisawa H, Cheng HJ, Ruhrberg C (2008). Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development. Dev.Biol., 324(1), 1 - 9. doi:10.1016/j.ydbio
    • Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B (2008). Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature, 453(7195), 662 - 666. doi:10.1038/nature06892
    • Schwarz Q, Vieira JM, Howard B, Eickholt BJ, Ruhrberg C (2008). Neuropilin 1 and 2 control cranial gangliogenesis and axon guidance through neural crest cells. Development, 135(9), 1605 - 1613. doi:10.1242/dev.034322
    • Tozer GM, Akerman S, Cross NA, Barber PR, Bjorndahl MA, Greco O, Harris S, Hill SA, Honess DJ, Ireson CR, Pettyjohn KL, Prise VE, Reyes-Aldasoro CC, Ruhrberg C, Shima DT, Kanthou C (2008). Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors. Cancer Res., 68(7), 2301 - 2311.

    2007

    • Vieira JM, Ruhrberg C, Schwarz Q (2007). VEGF signalling pathways in vertebrate development.
    • Vieira JM, Ruhrberg C, Schwarz Q (2007). VEGF signalling pathways in vertebrate development. In Ruhrberg C (Ed.), VEGF in Development (pp. 14 - 29). : Springer Science and Business Media with Landes Bioscience.
    • Rosenstein JM, Krum JM, Ruhrberg C (2007). VEGF in the nervous system. In Ruhrberg C (Ed.), VEGF in Development (pp. 91 - 99). : Springer Science and Business Media with Landes Bioscience.
    • Vieira JM, Schwarz Q, Ruhrberg C (2007). Role of the neuropilin ligands VEGF164 and Sema3A in neuronal and vascular patterning. In Chadwick DJ, Goode J (Ed.), Novartis Symposium NF283, Vascular Development (pp. 230 - 237). : John Wiley and Sons Ltd.
    • Vieira JM, Schwarz Q, Ruhrberg C (2007). Selective requirements for NRP1 ligands during neurovascular patterning. Development, 134, 1833 - 1843. doi:10.1242/dev.002402

    2006

    • Ruhrberg C, Shima DT (2006). Tumour Angiogenesis. In: The Molecular Biology of Cancer.. In Pelengaris S, Khan M (Ed.), The molecular biology of cancer (pp. 411 - 423). : Wiley-Blackwell.

    2004

    • Schwarz Q, Gu C, Fujisawa H, Sabelko K, Gertsenstein M, Nagy A, Taniguchi M, Kolodkin AL, Ginty DD, Shima DT, Ruhrberg C (2004). Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve. Genes and Development, 18(22), 2822 - 2834. doi:10.1101/gad.322904
    • Gerhardt H, Ruhrberg C, Abramsson A, Fujisawa H, Shima D, Betsholtz C (2004). Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Developmental Dynamics, 231(3), 503 - 509. doi:10.1002/dvdy.20148
    • Golding M, Ruhrberg C, Sandle J, Gullick WJ (2004). Mapping nucleolar and spliceosome localization sequences of neuregulin1-beta3. Experimental Cell Research, 299(1), 110 - 118. doi:10.1016/j.yexcr.2004.05.028

    2003

    • Ruhrberg C, Gavalas A, Livet J, Henderson CE, Krumlauf R (2003). Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes.. Development, 130(23), 5663 - 5679. doi:10.1242/dev.00802
    • Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A, Bowen S, Lalli G, Witherden AS, Hummerich H, Nicholson S, Morgan PJ, Oozageer R, Priestley JV, Averill S, King VR, Ball S, Peters J, Toda T, Yamamoto A, Hiraoka Y, Augustin M, Korthaus D, Wattler S, Wabnitz P, Dickneite C, Lampel S, Boehme F, Peraus G, Popp A, Rudelius M, Schlegel J, Fuchs H, Hrabe DAM, Schiavo G, Shima DT, Russ AP, Stumm G, Martin JE, EMC F (2003). Mutations in dynein link motor neuron degeneration to defects in retrograde transport.. Science, 300(5620), 808 - 812. doi:10.1126/science.1083129
    • Ruhrberg C (2003). Growing and shaping the vascular tree: multiple roles for VEGF. BioEssays, 25(11), 1052 - 1060. doi:10.1002/bies.10351
    • Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C (2003). VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. The Journal of Cell Biology, , - . doi:10.1083/jcb.200302047

    2002

    • Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H, Betsholtz C, Shima DT (2002). Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes and Development, 16(20), 2684 - 2698. doi:10.1101/gad.242002

    2001

    • Ruhrberg C, Watson R, Golding M, Shima DT (2001). Heparin-binding VEGF isoforms provide spatially-restricted cues controlling blood vessel pattern during embryogenesis.
    • Ruhrberg C (2001). Endogenous inhibitors of angiogenesis. J Cell Sci., 114(Pt 18), 3215 - 3216.

    2000

    • Maatta A, Ruhrberg C, Watt FM (2000). Structure and regulation of the envoplakin gene. J Biol.Chem., 275(26), 19857 - 19865.
    • Gavalas A, Ruhrberg C, Krumlauf R (2000). Abnormal motor neuron development in mice lacking anterior Hox genes.

    1999

    • Muller JM, Meyer HH, Ruhrberg C, Stamp GW, Warren G, Shima DT (1999). The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene. J Biol.Chem., 274(15), 10154 - 10162.
    • Risk JM, Ruhrberg C, Hennies H, Mills HS, Di Colandrea T, Evans KE, Ellis A, Watt FM, Bishop DT, Spurr NK, Stevens HP, Leigh IM, Reis A, Kelsell DP, Field JK (1999). Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): the integration of genetic and physical maps of the TOC region on 17q25. Genomics, 59(2), 234 - 242.

    1998

    • Duhig T, Ruhrberg C, Mor O, Fried M (1998). The human Surfeit locus. Genomics, 52(1), 72 - 78.
    • Ruhrberg C, Williamson JA, Maatta A, Watt FM (1998). The periplakin gene maps to 16p13.3 in human and 16A-B1 in mouse. Genomics, 49(1), 157 - 159.
    • Kiyokawa C, Ruhrberg C, Nie Z, Karashima T, Mori O, Nishikawa T, Green KJ, Anhalt GJ, DiColandrea T, Watt FM, Hashimoto T (1998). Envoplakin and periplakin are components of the paraneoplastic pemphigus antigen complex. J Invest Dermatol., 111(6), 1236 - 1238.

    1997

    • Ruhrberg C, Watt FM (1997). The plakin family: versatile organizers of cytoskeletal architecture. Curr.Opin.Genet.Dev., 7(3), 392 - 397. doi:10.1016/S0959-437X(97)80154-2
    • Ruhrberg C, Hajibagheri MA, Parry DA, Watt FM (1997). Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. J Cell Biol., 139(7), 1835 - 1849.

    1996

    • Ruhrberg C, Williamson JA, Sheer D, Watt FM (1996). Chromosomal localisation of the human envoplakin gene (EVPL) to the region of the tylosis oesophageal cancer gene (TOCG) on 17q25. Genomics, 37(3), 381 - 385.
    • Ruhrberg C, Watt FM (1996). Envoplakin, a new keratinocyte protein that is a cornified envelope precursor and belongs to the desmoplakin family..
    • Ruhrberg C, Hajibagheri MA, Simon M, Dooley TP, Watt FM (1996). Envoplakin, a novel precursor of the cornified envelope that has homology to desmoplakin. J Cell Biol., 134(3), 715 - 729.

    1993

    • Tavassoli M, Ruhrberg C, Beaumont V, Reynolds K, Kirkham N, Collins WP, Farzaneh F (1993). Whole chromosome 17 loss in ovarian cancer. Genes Chromosomes.Cancer, 8(3), 195 - 198.