Miguel Angel Valverde and José Manuel Fernández-Fernández

Group website

 

Research Outline

Our research focuses on ion channels, transporters and signaling in the context of cellular responses to oxidative, mechanical and osmotic stresses. Our work aims to translate our understanding of cellular physiology into better understanding of the mechanisms of human disease.

 

Research Lines

  • MECHANICA MEchano/osmosensitive CHAnNels in epIthelia, Cancer and Asthma.

The group led by Drs. Valverde and Fernández-Fernández focuses on the study of ion channels of the Transient Receptor Potential (TRP) and Piezo families, their molecular regulation and their role in epithelial physiology and pathology.

Ca2+ signalling is one of the earliest events in mechano/osmotic signal transduction and TRP (particularly TRPV4), PIEZO 1 and 2 ion channels are responsible for the generation of many of these Ca2+signals. Mechano/osmotic transduction appears to be a critical aspect in cancer cell growth, invasion and metastasis as these processes are related to tumor stiffness and migration through confined environments. Currently, we are characterizing the role of mechano/osmosensitive ion channels in the process of tumor invasion and/or metastasis.

  • Low-throughput evaluation of novel, selective CaV2.1 inhibitors in animal models of Familial Hemiplegic Migraine: modulation of excitatory neurotransmission and analysis of potential therapeutic value.

 

Team during 2017-18

  • Postdocs: Fanny Rubio-Moscardo, Selma A. Serra, Mercè Izquierdo and Pablo Doñate-Macian.
  • PhD students: Carlos Pardo-Pastor, Julia Carrillo and Marina Vogel.
  • Technicians: Cristina Plata.
     

Selected publications 2017-18

  • Jung C, Fernández-Dueñas V, Plata C, Garcia-Elias A, Ciruela F, Fernández-Fernández JM and Valverde MA (2018). Functional coupling of GABAA/B receptors and the channel TRPV4 mediates rapid progesterone signaling in the oviduct. Science Signaling 11(543). pii: eaam6558.

 

  • Doñate-Macian P, Jungfleisch J, Pérez-Vilaró G, Rubio-Moscardo F, Perálvarez-Marín A, Diez J and  Valverde M.A. (2018). The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity. Nature Communications (2018) 9:2307; DOI: 10.1038/s41467-018-04776-7

 

  • Pardo-Pastor C, Rubio-Moscardo C, Vogel-González M, Serra SA, Afthinos A, Mrkonjic S, Destaing O, Abenza JF, Fernández-Fernández JM, Trepat X, Albiges-Rizo C, Konstantopoulos K, Valverde MA (2018). Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. Proceedings of the National Academy of Sciences (U.S.A.) 115(8):1925-1930

 

  • Alpizar JA, Boonen B, Sanchez A, Jung C, López-Requena A, Naert R, Steelant B, Luyts K, Plata C, De  Vooght V, Vanoirbeek JAJ, Meseguer VE, Voets T, Alvarez JL,Hellings PW, Hoet PHM, Nemery B, Valverde MA and Talavera K (2017). TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells. Nature Communications 8(1):1059. doi: 10.1038/s41467-017-01201-3.