Our group aims to contribute to the understanding of the transcriptional response to hypoxia and angiogenesis as a main adaptive response, to exploit this knowledge to improve clinical management of pathologies in which tissue hypoxia is a common feature. Our current research goals are: (1) Characterization of the transcriptional response to hypoxia. Identification of the molecular mechanisms responsible for gene downregulation during hypoxia and gene regulatory networks involving HIFs. (2) Understanding the role of HIFs in the control of endothelial cell proliferation during angiogenesis induced by hypoxia. (3) Identification of polymorphisms affecting HIF binding sites and characterization of their contribution to disease inter-individual variability in cancer and cardiopulmonary diseases. To achieve these goals we use a combination of experimental and computational approaches and employ a wide array of experimental models including primary cultures of endothelial cells, stem cells and embryoid bodies . We make extensive use of genomic techniques including RNA-seq, ChIP-seq, targeted-genome sequencing and functional genomics, among others.
Maria Tiana, Barbara Acosta-Iborra, Laura Puente-Santamaría, Pablo Hernansanz-Agustin, Rebecca Worsley-Hunt, Norma Masson, Francisco García-Rio, David Mole, Peter Ratcliffe, Wyeth W. Wasserman, Benilde Jimenez and Luis del Peso. The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia. Nucleic Acids Res. 2018 Jan 9;46(1):120-133
Roche O, Deguiz ML, Tiana M, Galiana-Ribote C, Martinez-Alcazar D, Rey-Serra C, Ranz-Ribeiro B, Casitas R, Galera R, Fernández-Navarro I, Sánchez-Cuéllar S, Bernard V, Ancochea J, Wasserman WW, García-Rio F, Jimenez B, del Peso L. Identification of non-coding genetic variants in samples from hypoxemic respiratory disease patients that affect the transcriptional response to hypoxia. Nucleic Acids Res. 2016;44(19):9315-9330
Gómez-Maldonado L, Tiana M, Roche O, Prado-Cabrero A, Jensen L, Fernandez-Barral A, Guijarro-Muñoz I, Favaro E, Moreno-Bueno G, Sanz L, Aragones J, Harris A, Volpert O, Jimenez B, del Peso L. EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination. Oncogene. 2015 May 14;34(20):2609-20.
Ortiz-Barahona A, Villar D, Pescador N, Amigo J, del Peso L. Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction. Nucleic Acids Res. 2010 Apr;38(7):2332-45.
Pescador N, Cuevas Y, Naranjo S, Alcaide M, Villar D, Landázuri MO, Del Peso L. Biochem J. Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 [egln3/phd3] gene. 2005 Aug 15;390(Pt 1):189-97.