Piero Crespo Baraja (IP)

  • IBBTEC. Albert Einstein 22, PCTCAN, 39011 Santander
  • pedro.crespo@unican.es
  • 942 200959
  • Spatial Regulation of Ras-ERK Signals in Cancer
  • Director; Principal Investigator
  • Cancer
  • Department of Cell & Molecular Signalling

Piero Crespo obtained his BSc degree in Biology from Universidad Autónoma de Madrid (1986) and his Ph.D degree in Biochemistry and Molecular Biology from University of Cantabria in 1991. Always interested in signal transduction, in 1992 he moved to the United States as a Fulbright scholar, to join Silvio Gutkind's laboratory at the National Institutes of Health (Bethesda, USA). During his stay at NIH from 1992 to 1996, his main achievements were the unravelling of the role of beta-gamma dimers in the activation of the RAS-ERK pathway by G protein-coupled receptors and the identification of VAV as an exchange factor for RHO GTPases, both published in Nature as first author. He returned to Spain in 1996 with a "Contrato de Reincorporación" and gained tenure at the Spanish Research Council (CSIC) as a Staff Scientist in 1998, establishing his group at the Instituto de Investigaciones Biomédicas (IIB), in Madrid. In 2008 he was promoted to Full Professor. In 2007 his group was selected as one of the ten groups that constituted the embryo of the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) and moved to Santander. Currently, he is the director of the institute. Prof. Crespo's research has been always focused on the regulation of the RAS-ERK pathway, in particular on how subcellular localization and signal compartmentalization affect the biochemical and biological outputs of this signalling route, both in physiological and pathological contexts, in particular in cancer, and how space-regulated effects can be exploited as antineoplastic strategies. Prof. Crespo has authored 98 peer-reviewed publications in SCI journals, including: Nature, Science, Cancer Cell, Molecular Cell, Nature Cell Biology, Nature Communications, EMBO J., J Cell. Biol, among 55 publicaction as first or principal author. Throughout his career he has been regularly funded by national and international grants, including two EU FP6 grants and an AICR project. Currently, he coordinates a 1.2 million € AECC project and he is a member of CIBERONC. He has mentored 12 doctotal theses, two were awarder University of Cantabria "Premio Extraordinario de Doctorado". He has been honoured by four national and international research awards. He serves in five editorial boards and acts as a reviewer for numerous scientific journals and granting agencies. He has been invited as a speaker to more than 100 meetings, workshops and seminar series in numerous national and international universities and scientific institutions. 

​Spatial Regulation of Ras-ERK Signals in Cancer


Research lines 

    • Spatial regulation of Ras-ERK signals in physiological processes and in cancer
    • Development of antitumoral drugs targeting protein-protein interactions in the Ras-ERK pathway


Funding

    • "Las interacciones entre proteínas scaffolds y dímeros de ERK como dianas antitumorales". BFU2011-23807. 2012-2015.
    • “Nuevas dianas moleculares en la ruta Ras-ERK: potencial terapéutico en el cáncer de tiroides”. Asociación Española Contra el Cáncer (AECC). GCB141423113. Proyecto coordinado 2014-2019. 
    • Red Temática de Investigación Cooperativa sobre el Cáncer (RTICC). RD/12/0036/0033. 2012-2015.
    • “Proteínas Scaffold como moduladores de la resistencia a inhibidores de la ruta RAS-ERK en melanoma”.  SAF-2015 63638R.  2016-2018.

isciiPiero.png

GRUPO FINANCIADO POR LA RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN CÁNCER DEL ISCIII/FEDER (RD12/0036/0033). 2012-2016  
Grupo incluído en el programa: Molecular Mechanisms in Cancer. Involucrado en el desarrollo de nuevas estratégias terapéuticas para inhibir rutas de señalización pro-tumorales.


ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer

Moreno, T., Monterde, B., González-Silva, L. et al.

​Oncogene (2021). https://doi.org/10.1038/s41388-021-01748-y

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RAS Subcellular Localization Inversely Regulates Thyroid Tumor Growth and Dissemination

RAS Subcellular Localization Inversely Regulates Thyroid Tumor Growth and Dissemination

Yaiza García-Ibáñez, Garcilaso Riesco-Eizaguirre, Pilar Santisteban, Berta Casar and Piero Crespo

​Cancers (Basel). 2020 Sep 10;12(9):E2588. doi: 10.3390/cancers12092588.

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Regulators of the RAS-ERK pathway as therapeutic targets in thyroid cancer.

​Zaballos MA, Acuña-Ruiz A, Morante M, Crespo P, Santisteban P.

Endocr Relat Cancer. 2019 Apr 1. pii: ERC-19-0098.R1. doi: 10.1530/ERC-19-0098.

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An Integrated Global Analysis of Compartmentalized HRAS Signaling.

An Integrated Global Analysis of Compartmentalized HRAS Signaling.

Santra T, Herrero A, Rodriguez J, von Kriegsheim A, Iglesias-Martinez LF, Schwarzl T, Higgins D, Aye TT, Heck AJR, Calvo F, Agudo-Ibáñez L, Crespo P, Matallanas D, Kolch W.

​Cell Rep. 2019 Mar 12;26(11):3100-3115.e7. doi: 10.1016/j.celrep.2019.02.038.

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The RAS-ERK pathway: A route for couples.

The RAS-ERK pathway: A route for couples.

Santos E, Crespo P.

Sci Signal. 2018 Oct 30;11(554). pii: eaav0917. doi: 10.1126/scisignal.aav0917.

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RAS at the Golgi antagonizes malignant transformation through PTPRκ-mediated inhibition of ERK activation.

Casar B, Badrock AP, Jiménez I, Arozarena I, Colón-Bolea P, Lorenzo-Martín LF, Barinaga-Rementería I, Barriuso J, Cappitelli V, Donoghue DJ, Bustelo XR, Hurlstone A, Crespo P.

​Nat Commun. 2018 Sep 5;9(1):3595. doi: 10.1038/s41467-018-05941-8.

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Protein-Protein Interactions: Emerging Oncotargets in the RAS-ERK Pathway

García-Gómez R, Bustelo XR, Crespo P.

​Trends Cancer. 2018 Sep;4(9):616-633. doi: 10.1016/j.trecan.2018.07.002. Epub 2018 Aug 9. 

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RAS GTPase-dependent pathways in developmental diseases: old guys, new lads, and current challenges.

Bustelo XR, Crespo P, Fernández-Pisonero I, Rodríguez-Fdez S.

​Curr Opin Cell Biol. 2018 Dec;55:42-51. doi: 10.1016/j.ceb.2018.06.007. Epub 2018 Jul 11.

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Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains.

Zhang L, Zhang P, Wang G, Zhang H, Zhang Y, Yu Y, Zhang M, Xiao J, Crespo P, Hell JW, Lin L, Huganir RL, Zhu JJ.

Neuron. 2018 May 16;98(4):783-800.e4. doi: 10.1016/j.neuron.2018.03.049. Epub 2018 Apr 26.

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Characterisation of HRAS local signal transduction networks using engineered site-specific exchange factors

Herrero A, Reis-Cardoso M, Jimenez-Gomez I, Doherty C, Agudo Ibanez L, Pinto A, Calvo F, Kolch W, Crespo P, Matallanas DG

​Small GTPases Nov 26:1-13. 

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ERK Signals: Scaffolding Scaffolds?

Casar B, Crespo P. Front Cell Dev Biol. 2016 May 31; 4:49.

[PubMed]

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The chick embryo chorioallantoic membrane as an in vivo model to study metastasis.

Crespo P., and Casar B. Bio-protocol Vol 6, Iss 20, Oct 20, 2016 DOI:10.21769/

http://bio-protocol.org/e1962.

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Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells.

Herrero A, Casar B, Colón-Bolea P, Agudo-Ibáñez L, Crespo P. Mol Biol Cell. 2016 Apr 20.

[PubMed]

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Absence of K-Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts.

Muñoz-Félix JM, Fuentes-Calvo I, Cuesta C, Eleno N, Crespo P, López-Novoa JM, Martínez-Salgado C. J Cell Physiol. 2016 Feb 12. [Epub ahead of print]

[PubMed]

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Tumors topple when ERKs uncouple.

Herrero A, Crespo P. Mol Cell Oncol. 2015 Oct 29;3(2):e1091875. eCollection 2016 Mar.

[PubMed]

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Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.

Herrero A, Pinto A, Colón-Bolea P, Casar B, Jones M, Agudo-Ibáñez L, Vidal R, Tenbaum SP, Nuciforo P, Valdizán EM, Horvath Z, Orfi L, Pineda-Lucena A, Bony E, Keri G, Rivas G, Pazos A, Gozalbes R, Palmer HG, Hurlstone A, Crespo P.

​Cancer Cell. 2015 Aug 10 [PubMed]

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H-Ras distribution and signaling in plasma-membrane microdomains are regulated by acylation and deacylation events.

Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P. Mol Cell Biol. 2015 Mar 16.

[PubMed]

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Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway.

Colón-Bolea P, Crespo P. Bioessays. 2014 Dec;36(12):1162-9.

[PubMed]

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Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis.

Baschieri F, Confalonieri S, Bertalot G, Di Fiore PP, Dietmaier W, Leist M, Crespo P, Macara IG, Farhan H. Nat Commun. 2014 Sep 11;5:4839.

[PubMed]

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The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration in fibroblasts.

Fuentes-Calvo I, Crespo P, Santos E, López-Novoa JM, Martínez-Salgado C. Biochim Biophys Acta. 2013 Dec;1833(12):2734-44.

[PubMed]

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Mxi2 sustains ERK1/2 phosphorylation levels in the nucleus by preventing ERK1/2 binding to phosphatases.

Casar B., Rodríguez J., Gibor G., Seger R., and Crespo P. Biochem. J., 441, 571-578. (2012).

​[pubmed]

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Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.

Matallanas D., Romano D., Al-Mulla F., O'Neil E., Al-Ali W, Crespo P., Doyle B, Nixon B, Samson O, Drosten M., Barbacid M., and Kolch W. Mol. Cell, 44, 893-906. (2011).

​[pubmed]

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Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.

Matallanas D, Romano D, Al-Mulla F, O'Neill E, Al-Ali W, Crespo P, Doyle B, Nixon C, Sansom O, Drosten M, Barbacid M, Kolch W. Mol Cell. 2011 Dec 23;44(6):893-906.

[PubMed]

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Working without kinase activity: phosphotransfer-independent functions of extracellular signal-regulated kinases.

Rodríguez J, Crespo P. Sci Signal. 2011 Oct 25;4(196):re3.

[PubMed]

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Ras and Rho GTPases on the move: The RasGRF connection.

Crespo P, Calvo F, Sanz-Moreno V. Bioarchitecture. 2011 Jul;1(4):200-204.

[PubMed]

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Ras GEFs as inhibitors of Rho GTPases: RasGRF suppresses Cdc42-mediated tumor cell movement, cytoskeletal dynamics and transformation.

Calvo F., Sanz-Moreno V, Agudo-Ibáñez L., Wallberg F., Sahai E., Marshall C.J., and Crespo P. Nat. Cell Biol. 13, 819-826. (2011). (Seleccionado por The Faculty of 1000).

​[pubmed]

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An actor on many stages: Ras subcellular localization, site-specific regulation and functions

Arozarena I., Calvo F., Agudo-Ibañez L. and Crespo P. Genes & Cancer. 182-194. (2011).

​[pubmed]

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RasGRF negatively regulates Cdc42-mediated transformation, cytoskeletal dynamics and tumor cell movement

Calvo F, Sanz-Moreno V, Agudo-Ibáñez L, Wallberg F, Sahai E, Marshall CJ and Crespo P.

​Nature Cell Biology13(7):819-26. 

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Activation of Ras and Rho GTPases and MAP kinases by G-Protein-coupled receptors

Chiariello M., Vaqué J.P., Crespo P., and Gutkind J.S. Meths. Mol. Biol. 661, 137-150. (2010).

​[pubmed]

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New druggable targets in the Ras pathway?

Matallanas D., and Crespo P. Curr. Opin. Mol. Ther. 12, 674-683. (2010).

​[pubmed]

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Analysis of ERKs dimerization by electrophoresis.

Pinto A. and Crespo P. Methods. Mol. Biol. 661, 335-342. (2010).

​[pubmed]

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ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of Retinoblastoma–LaminA complexes.

Rodríguez J., Calvo F., González J.M., Casar B., Andrés V. and Crespo P. J. Cell Biol. 191, 967-979. (2010). (Editorial en el mismo número; Editorial en Science Sig. 3, ec371 2010; Seleccionado por The Faculty of 1000).

​[pubmed]

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The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumour therapies

Calvo F., Agudo-Ibáñez L., and Crespo P. Bioessays. 32, 412-421. (2010).

​[pubmed]

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Correction for Agudo-Ibáñez et al., "H-Ras Distribution and Signaling in Plasma Membrane Microdomains Are Regulated by Acylation and Deacylation Events"

Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P.

​Mol Cell Biol. 2018 Aug 15;38(17). pii: e00335-18. doi: 10.1128/MCB.00335-18. Print 2018 Sep 1.

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Lorena Agudo Ibáñez

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Vincenzo Cappitelli

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Dalia de la Fuente Vivas

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Rocío García Gómez

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Marta Morante Ezquerra

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Alicia Noriega Tato

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Laura Ruiz Peinado

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