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Prof Christiana Ruhrberg
Personal Profile
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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
- 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
- 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
- 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, 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.
- 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.
- 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
- 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
- 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
- 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.
- Mackenzie F, Ruhrberg C (2012). Diverse roles for VEGF-A in the nervous system.. Development, 139(8), 1371 - 1380. doi:10.1242/dev.072348
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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 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
- 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, 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
- 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
- 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.
- 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.
- 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, 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
- 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
- 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
- Ruhrberg C, Maden C, Schwarz Q (2009). Neuropilin 1 controls cardiovascular development through neural crest cells. FASEB JOURNAL, 23, - .
- 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
- Maden C, Schwarz Q, Ruhrberg C (2009). Neuropilin signalling controls sequential stages of sympathetic development. doi:10.1016/j.mod.2009.06.583
- 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
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- Ruhrberg C (2001). Endogenous inhibitors of angiogenesis. J Cell Sci., 114(Pt 18), 3215 - 3216.
- Ruhrberg C, Watson R, Golding M, Shima DT (2001). Heparin-binding VEGF isoforms provide spatially-restricted cues controlling blood vessel pattern during embryogenesis.
- Gavalas A, Ruhrberg C, Krumlauf R (2000). Abnormal motor neuron development in mice lacking anterior Hox genes.
- Maatta A, Ruhrberg C, Watt FM (2000). Structure and regulation of the envoplakin gene. J Biol.Chem., 275(26), 19857 - 19865.
- 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.
- 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.
- 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.
- 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, 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, 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.
- Ruhrberg C, Watt FM (1996). Envoplakin, a new keratinocyte protein that is a cornified envelope precursor and belongs to the desmoplakin family..
- 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.
- Ruhrberg C, Raimondi C, Wall I, Uniewicz K, Fernig D (). Defining novels roles for NRP1 in angiogenesis. doi:10.1007/s10456-012-9326-5
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