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Groupleader: Carmen Ruiz de Almodóvar

Molecular and Cellular Mechanisms of the Neurovascular link 

Group Leader Carmen Ruiz de Almodóvar

Carmen Ruiz de Almodóvar

Molecular and Cellular Mechanisms of the Neurovascular link

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Research 


New address:

Dept. Vascular Dysfunktion
Neuro-Vascular Lab (ECAS)
European Center for Angioscience
Endothelial Lab
Institute for Transfusion Medicine/Immunology
Ludolph-Krehl-Str. 13-17, D-68167 Mannheim

https://www.umm.uni-heidelberg.de/vascular-dysfunction/​

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Despite their distinct functions, the nervous and vascular systems regulate each other function and share many more similarities and common principles than previously expected. For example, at the tip of a growing vessel there is a specialized endothelial cell called endothelial tip cell, which senses the cues in the environment and leads the sprouting vessel to its final destination. Similarly, at the leading edge of a growing axon there is a specialized structure termed the growth cone, responsible for sensing and responding to the guidance cues that
will guide the axon to its final target. Interestingly, typical axon guidance cues
are also known to regulate blood vessel guidance. Conversely, for example, the
key angiogenic factor, vascular endothelial growth factor (VEGF), and its
receptors, are expressed in neuronal cells and participate in processes such as
neuronal migration and axon guidance. Despite these initial findings, still little
is known about the biology of angiogenic factors in neurons, the signaling
pathways that they activate and their functional role in neurodevelopment.

In our lab, we are interested in understanding (i) the signaling pathways and cellular mechanisms that angiogenic molecules exert in neuronal cells and (ii) the communication between the vascular and nervous systems during development. For this, we are using a combination of mouse genetics, organotypic cultures, cell biology, biochemistry and molecular biology approaches.

Determining how the vascular system, influence neuronal wiring will shed new light in the understanding of the molecular control of neuronal development and the possible causes of neurodevelopmental disorders. Research in this field may suggest new strategies to treat those disorders and to promote axon regeneration after injury or disease.



Download BZH-Report Ruiz de Almodóvar 2014-2016

CV 


1994 – 1999
 
University of Granada, Spain, Biochemistry Degree
 
1999 – 2004

 
PhD in Biochemistry and Molecular Biology, Institute of Parasitology and
Biomedicine, CSIC, Granada, Spain (Lab. of Prof. A. López-Rivas)
 
2004 – 2011
 
Postdoctoral fellow at the Vesalius Research Center, VIB-KU Leuven,
Leuven, Belgium (Lab. of Prof. P. Carmeliet)

Jan. 2011–
April.2011
 
Visiting scientist at Genentech, San Francisco, CA. USA
(Lab. of Prof. M. Tessier-Lavigne)
June 2011 - Junior Group Leader, BZH, University of Heidelberg


AcademiaNet Profile



 
 

Publications 


Blood vessels as regulators of neural stem cell properties. Front Mol Neurosci.
Karakatsani A , Shah B, Ruiz de Almodovar C. (2019)

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation. Int J Cancer. In press.
Stöth M, Freire Valls A, Chen M, Hidding S, Knipper K, Shen Y, Klose J, Ulrich A, Ruiz de Almodovar C, Schneider M, Schmidt T. (2019)

A PRDX1-p38α heterodimer amplifies MET-driven invasion of IDH-wildtype and IDH-mutant gliomas. Int J Cancer.
Wirthschaft P, Bode J, Simon AEM, Hoffmann E, van Laack R, Krüwel T, Dietrich F, Bucher D, Hahn A, Sahm F, Breckwoldt MO, Kurz FT, Hielscher T, Fischer B, Dross N, Ruiz de Almodovar C, von Deimling A, Herold-Mende C, Plass C, Boulant S, Wiestler B, Reifenberger G, Lichter P, Wick W, Tews B. (2018)

Neurovascular Communication during CNS Development. Dev Cell. 45(1):10-32.
Paredes I, Himmels P, Ruiz de Almodóvar C. (2018)

Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation. J Cell Mol Med. 22(11):5244-5256.
Atienzar-Aroca S, Serrano-Heras G, Freire Valls A, Ruiz de Almodovar C, Muriach M, Barcia JM, Garcia-Verdugo JM, Romero FJ, Sancho-Pelluz J. (2018)

Unconventional Secretion Mediates the Trans-cellular Spreading of Tau. Cell reports, 23(7), 2039–2055. https://doi.org/10.1016/j.celrep.2018.04.056 Katsinelos, T., Zeitler, M., Dimou, E., Karakatsani, A., Müller, H.M., Nachman, E., Steringer, J.P., Ruiz de Almodovar, C., Nickel, W., & Jahn, T.R. (2018)

CNS Macrophages Control Neurovascular Development via CD95L. Cell Rep. 19(7):1378-1393
Chen S, Tisch N, Kegel M, Yerbes R, Hermann R, Hudalla H, Zuliani C, Gülcüler GS, Zwadlo K, von Engelhardt J, Ruiz de Almodóvar C, Martin-Villalba A. (2017)

Motor neurons control blood vessel patterning in the developing spinal cord. Nat Commun. 8:14583.
Himmels P, Paredes I, Adler H, Karakatsani A, Luck R, Marti HH, Ermakova O, Rempel E, Stoeckli ET & Ruiz de Almodovar C. (2017)

Neuronal LRP4 regulates synapse formation in the developing CNS. Development.
Karakatsani A, Marichal N, Urban S, Kalamakis G, Ghanem A, Schick A, Zhang Y, Conzelmann KK, Rüegg MA, Berninger B, Ruiz de Almodovar C, Gascón S, Kröger S. (2017)

RIPK1/RIPK3 promotes vascular permeability to allow tumor cell extravasation independent of its necroptotic function. Cell Death Dis. 8(2):e2588.
Hänggi K, Vasilikos L, Freire Valls A, Yerbes R, Knop J, Spilgies L, Rieck K, Misra T, Bertin J, Gough PJ, Schmidt T, Ruiz de Almodovar C & Wong WW. (2017)

YAP/TAZ orchestrate VEGF signaling during developmental angiogenesis. Dev Cell. 42(5):462-478.e7. Wang X, Freire Valls A, Shermann G, Shen Y, Moya IM, Castro L, Urban S, Solecki GM, Winkler F, Riedemann Lm Jain RK, Mazzone M, Schmidt T, Fischer T, Halder G, Ruiz de Almodovar C. (2017)

TAM receptors Tyro3 and Mer as novel targets in colorectal cancer. Oncotarget. Aug 30;7(35):56355-56370. doi: 10.18632/oncotarget.10889.
Schmitz R, Freire Valls A, Yerbes R, von Richter S, Kahlert C, Loges S, Weitz J, Schneider M, Ruiz de Almodovar C, Ulrigh A, Schmidt T. (2016)

The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A. Cell Rep. 14(11):2653-67.
Segura I, Lange C, Knevels E, Moskalyuk A, Pulizzi R, Eelen G, Chaze T, Tudor C, Boulegue C, Holt M, Daelemans D, Matondo M, Ghesquière B, Giugliano M, Ruiz de Almodovar C, Dewerchin M & Carmeliet P. (2016)

Vascular endothelial growth factor: a neurovascular target in neurological diseases. Nat Rev Neurol. 12(8):439-54.
Lange C, Storkebaum E, Ruiz de Almodovar C, Dewerchin M & Carmeliet P. (2016)

Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma. Oncotarget. 6(31):31050-68.
Kessler T, Sahm F, Blaes J, Osswald M, Rübmann P, Milford D, Urban S, Jestaedt L, Heiland S, Bendszus M, Hertenstein A, Pfenning PN, Ruiz de Almodóvar C, Wick A, Winkler F, von Deimling A, Platten M, Wick W, Weiler M. (2015)

Human mesenchymal stem cells enhance the systemic effects of radiotherapy. Oncotarget. 6(31):31164-80.
Farias VA, O'Valle F, Lerma BA, Ruiz de Almodóvar C, López-Peñalver JJ, Nieto A, Santos A, Fernández BI, Guerra-Librero A, Ruiz-Ruiz MC, Guirado D, Schmidt T, Oliver FJ, Ruiz de Almodóvar JM. (2015)

Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol. Nat Commun 6, 7688. https://doi.org/10.1038/ncomms8688 Hacke, M., Björkholm, A., Hellwig, P., Himmels, P., Ruiz de Almodóvar, C., Brügger, B., Wieland, F., & Ernst, A.M. (2015)

The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells. Cell Rep. 12(11):1761-73.
Savant S, La Porta S, Budnik A, Busch K, Hu J, Tisch N, Korn C, Valls AF, Benest AV, Terhardt D, Qu X, Adams RH, Baldwin HS, Ruiz de Almodóvar C, Rodewald HR, Augustin HG. (2015)

Inhibition of Tumor Angiogenesis and Growth by a Small-Molecule Multi-FGF Receptor Blocker with Allosteric Properties. Cancer Cell. 23(4):477-488.
Bono F, De Smet F, Herbert C, De Bock K, Georgiadou M, Fons P, Tjwa M, Alcouffe C, Ny A, Bianciotto M, Jonckx B, Murakami M, Lanahan AA, Michielsen C, Sibrac D, Dol-Gleizes F, Mazzone M, Zacchigna S, Herault JP, Fischer C, Rigon P, Ruiz de Almodovar C, Claes F, Blanc I, Poesen K, Zhang J, Segura I, Gueguen G, Bordes MF, Lambrechts D, Broussy R, van de Wouwer M, Michaux C, Shimada T, Jean I, Blacher S, Noel A, Motte P, Rom E, Rakic JM, Katsuma S, Schaeffer P, Yayon A, Van Schepdael A, Schwalbe H, Gervasio FL, Carmeliet G, Rozensky J, Dewerchin M, Simons M, Christopoulos A, Herbert JM, Carmeliet P. (2013)

Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell, 152(5):1065-76. (*These authors contributed equally)
Snuderl M*, Batista A*, Kirkpatrick ND*, Ruiz de Almodovar C*, Riedemann L, Walsh EC, Anolik R, Huang Y, Martin JD, Kamoun W, Knevels E, Schmidt T, Farrar CT, Vakoc BJ, Mohan N, Chung E, Roberge S, Peterson T, Bais C, Zhelyazkova BH, Yip S, Hasselblatt M, Rossig C, Niemeyer E, Ferrara N, Klagsbrun M, Duda DG, Fukumura D, Xu L, Carmeliet P, Jain RK. (2013)

The NADPH oxidase Nox2 regulates VEGFR1/CSF-1R-mediated microglial chemotaxis and promotes early postnatal infiltration of phagocytes in the subventricular zone of the mouse cerebral cortex. Glia. 61(9):1542-55.
Lelli A, Gervais A, Colin C, Chéret C, Ruiz de Almodovar C, Carmeliet P, Krause KH, Boillée S, Mallat M. (2013)

VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci. 70(10):1763-78.
Carmeliet, P, Ruiz de Almodovar, C. (2013)

VEGF mediates commissural axon chemoattraction through its receptor Flk1. Neuron (70):966-78. (*These authors contributed equally)
Ruiz de Almodovar, C*, Fabre, P*, Knevels, E, Coulon, C, Segura, I, Haddick, PCG, Aerts, L, Delattin, N, Strasser, G, Oh, WJ, Lange, C, Vinckier, S, Haigh, JJ, Fouquet, C, Henderson, C, Gu C, Alitalo K, Castellani V, Tessier-Lavigne M, Chedotal A, Charron F* and Carmeliet P*. (2011)

VEGF modulates NMDA receptor activity via a Src-family-kinase-dependent cross-talk. Proc Natl Acad Sci U S A. 108(33):13782-7. (*These authors contributed equally)
Meissirel, C*, Ruiz de Almodovar, C*, Knevels, E*, Coulon, C, Chounlamountri, N, Segura, I, de Rossi, P, Vinckier, S, Anthonis, K, Deléglise, B, de Mol, M, Ali, C, Dassonville, K, Loyens, E, Honnorat, J, Michotte, Y, Rogemond, V, Smolders, I, Voets, T, Vivien, D, Vanden Berghe, P, Van Den Bosch, L, Robberecht, W, Chédotal, A, Oliviero, S, Dewerchin, M, Schmucker, D, Thomasset, N, Salin, PA, & Carmeliet, P. (2011)

An epithelial-endothelial crostalk regulates differentiation in developing pancreas. Dev Biol 347(1): 216-27.
Pierreux, CE, Cordi, S, Hick, AC, Ruiz de Almodovar, C, Courtoy, PJ, Carmeliet, P & Lemaigre, FP. (2010)

Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation 122(3):273-81. (*These authors contributed equally)
Storkebaum, E*, Ruiz de Almodovar, C*, Meens, M, Zacchigna, S, Mazzone, M, Vanhoutte, G, Vinckier, S, Poesen, K, Lambrechts, D, Janssen, G, Fazzi, GE, Schiffers, PM, Rohrer, H, Van der Linden, A, DeMey, J. & Carmeliet, P. (2010)

Matrix-binding VEGF isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. J. Neurosci 30(45): 15052-66. (*These authors contributed equally)
Ruiz de Almodovar, C*, Coulon, C*, Knevels, E, Salin, PA, Chounlamountri, N, Poesen, K, Hermans, K, Lambrechts, D, Van Geyte, K, Dhondt, J, Dresselaers, T, Renaud, J, Aragones, J, Zacchigna, S, Geudens, I, Gall, D, Stroobants, S, Mutin, M, Dassonville, K, Storkebaum, E, Jordan, BJ, Eriksson, U, Moons, L, D’Hooge, R, Haigh, JJ, Belin, MF, Schiffmann, S, Van Hecke, P, Gallez, B, Chedotal, A, Honnorat, J, Thomasset, N, Carmeliet, P, and Meissirel, C. (2010)

Role of Dll4/Notch in the formation and wiring of the lypmphatic network in zebrafish. Arterioscler Thromb Vasc Biol. (9):1605-702.
Geudens, I, Herpers, R, Hermans, K, Segura, I, Ruiz de Almodovar, C, Bussmann, J, De Smet, F, Vandevelde, W, Hogan, BM, Siekmann, A, Claes, F, Moore, J, Pistocchi, AS, Loges, S, Mazzone, M, Mariggi, MG, Bruyère, F, Cotelli, F, Kerjaschki, D, Noël, A, Foidart, J, Gerhardt, H, Ny, A, Langenberg, T, Lawson, N, Duckers, HJ, Schulte-Merker, S, Carmeliet, P. and Dewerchin, M. (2010)

Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136(5):839-51.
Mazzone, M, Dettori, D, Leite de Oliveira, R, Loges, S, Schmidt, T, Jonckx, B, Tian, YM, Lanahan, AA, Pollard, P, Ruiz de Almodovar, C, De Smet, F, Vinckier, S, Aragones, J, Luttun, A, Wyns, S, Jordan, B, Pisacane, A, Gallez, B, Lampugnani, MG, Dejana, E, Simons, M, Ratcliffe, P, Maxwell, P. & Carmeliet, P. (2009)

Role and theraputical potential of VEGF in the nervous system. Physiol Rev 89(2): 607-48.
Ruiz de Almodovar, C, Lambrechts, D, Mazzone, M & Carmeliet, P. (2009)

The neurovascular link in health and disease: an update. Trends Mol Med. 15(10):439-51.
Segura, I, De Smet, F, Hohensinner, PJ, Ruiz de Almodovar, C. & Carmeliet, P. (2009)

Angiogenesis in the central nervous system. Book chapter in the book titled: Angiogenesis: an integrative approach from science to medicine. Edited by Figg and Folkman, Springer 489-504. (*These authors contributed equally)
Ruiz de Almodovar, C*, Zacchigna, S* & Carmeliet, P. (2008)

Similarities between angiogenesis and neural development: what small animal models can tell us. Curr Top Dev Biol 80:1-55. (*These authors contributed equally)
Zacchigna, S*, Ruiz de Almodovar, C* & Carmeliet, P. (2008)

Buiding in resistance to cell death. Nat Genet Nov; 39(11):1308-1309.
Mazzone, M, Ruiz de Almodovar, C, Carmeliet, P. (2007)

General concepts of angiogenesis and vasculogenesis. Book chapter for the book titled “Retinal vascular disease”. Edited by Joussen, Gardner Kirchhof & Ryan. Springer 38-65. (*These authors contributed equally)
Ruiz de Almodovar, C*, Ny, A* & Carmeliet, P. (2007)

Guidance of Vascular and Neuronal Network Formation. Book chapter for the book titled “Tumor angiogenesis: Mechanisms and Cancer therapy”. Edited by Marmé, Fusenig and Norbert. Springer 2007: 47-65. (*These authors contributed equally)
Ruiz de Almodovar, C*, Zacchigna, S*, Autiero, M & Carmeliet, P. (2007)

Vascular and Neural development, intersecting parallelisms and crossroads. Book chapter for the book titled: Therapeutic Neovascularization-Quo Vadis?. Edited by Deindl and Kupatt. Springer 159-191.
Zacchigna, S, Ruiz de Almodovar, C, Lafuste, P & Carmeliet, P. (2007)

A new mouse model to study acquired lymphedema. PLoS Med, Jul; 3(7):e264.
Schenider, M, Ny, A, Ruiz de Almodovar, C & Carmeliet P. (2006)

An SDF-1 trap for myeloid cells stimulates angiogenesis. Cell 124, 18-21.
Ruiz de Almodovar, C, Luttun, A & Carmeliet, P. (2006)

Non-angiogenic functions of VEGF. Book chapter for the book titled “Angiogenesis: From Basic Science to Clinical Aspects”. Edited by N. Ferrara. CRC Taylor & Francis 133-155.
Haigh, JJ, Ruiz de Almodovar, C, Schneider, M & Carmeliet, P. (2006)

Selective regulation of arterial branching morphogenesis by synectin. Dev Cell, Jun;10(6):783-95.
Chittenden, TW, Claes, F, Lanahan, AA, Autiero, M, Palac, RT, Tkachenko, EV, Elfenbein, A, Ruiz de Almodovar, C, Dedkov, E, Tomanek, R, Li, W, Westmore, M, Singh, J, Horowitz, A, Mulligan-Kehoe, MJ, Moodie, KL, Zhuang, ZW, Carmeliet, P & Simons, M. (2006)

Interferon-gamma and TRAIL in human breast tumor cells, Vitam Horm, 67, 291-318.
Ruiz de Almodovar, C, Lopez-Rivas, A & Ruiz-Ruiz, C. (2004)

The up-regulation of human caspase-8 by interferon-gamma in breast tumor cells requires the induction and action of the transcription factor interferon regulatory factor-1, J Biol Chem, 279, 19712-20.
Ruiz-Ruiz, C, Ruiz de Almodovar, C, Rodriguez, A, Ortiz-Ferron, G, Redondo, J. M. & Lopez-Rivas, A. (2004)

Transcriptional regulation of the TRAIL-R3 gene, Vitam Horm, 67, 51-63.
Ruiz de Almodovar, C, Lopez-Rivas, A, Redondo, J. M. & Rodriguez, A. (2004)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding site, J Biol Chem, 279, 4093-101.
Ruiz de Almodovar, C, Ruiz-Ruiz, C, Rodriguez, A, Ortiz-Ferron, G, Redondo, J. M. & Lopez-Rivas, A. (2004)

Inhibition of glucose metabolism sensitizes tumor cells to death receptor-triggered apoptosis through enhancement of death-inducing signaling complex formation and apical procaspase-8 processing, J Biol Chem, 278, 12759-68.
Munoz-Pinedo, C, Ruiz-Ruiz, C, Ruiz de Almodovar, C, Palacios, C & Lopez-Rivas, A. (2003)

Death on the beach: a rosy forecast for the 21st century, Cell Death Differ, 9, 1026-9. (*These authors contributed equally)
Munoz-Pinedo, C*, Ruiz de Almodovar, C* & Ruiz-Ruiz, C*. (2002)

Transcription initiation sites and promoter structure of the human TRAIL-R3 gene, FEBS Lett, 531, 304-8.
Ruiz de Almodovar, C, Lopez-Rivas, A, Redondo, J. M. & Rodriguez, A. (2002)

The differential sensitivity of Bcl-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bcl-2 protein levels, Oncogene, 20, 7128-33.
Ruiz de Almodovar, C, Ruiz-Ruiz, C, Munoz-Pinedo, C, Robledo, G & Lopez-Rivas, A. (2001)

Working in the lab 


Funding 


Alumni 


LAB ALUMNI 

Rosario Yerbes (Postdoc 2012 - 2015)  - Current position: Senior postdoc at Cabimer (Sevilla, Spain)

Severino Urban (PhD student 2011 - 2016) - Current position: Consultant at Gempex GMBH

Patricia Himmels (PhD student 2013-2017) - Current position: Postdoc at Genentech (San Francisco, USA)

Xiaohong Wang (Postdoc 2013-2018) - Current position: Full professor at Tianjin Medical University, China

Contact



Heidelberg University
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg

E-Mail:
carmen.ruizdealmodovar@medma.uni-heidelberg.de


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