My research has been focused in the structure and function relationships of several proteins, expanding from enzymes of the intermediary metabolism towards receptors, the prion protein and vimentin. We obtained some of the first structures of enzymes of mammalian methionine metabolism and analyzed the existence of signals or determinants for their subcellular distribution. Our main interest has been always related to redox stress and its influence on the behavior of different proteins through changes in activity, subcellular localization, inclusion/deletion of posttranslational modifications, alterations in protein-protein interactions, etc. Moreover, this interest in redox stress made us analyze its link to a variety of pathological states, among others acute liver injury, Wilson disease, hearing loss and neurodegenerative diseases. We have also explored the impact of nutrition on several parameters such as expression, protein levels, activity, etc. in the context of its putative impact on physiological impairments (i.e. hearing loss) and/or the ability of certain essential nutrients to prevent or delay the onset of certain pathologies.
Our laboratory is well known for its expertise in the analysis of posttranslational modifications, especialy oxidative modifications. We have a broad background in protein expression and purification, mutagenesis, analysis of subcellular localization and the methionine and homocysteine metabolism. Protein folding and stability studies are also performed in our laboratory.
Our fundamental interest is to contact groups with expertise in complementary field such as MS-imaging, especially at subcellular level, MS spectrometry and superresolution techniques.
Modulation of GSTP1-1 oligomerization by electrophilic inflammatory mediators and reactive drugs. Sánchez-Gómez, F.J., García-Dorado, C., Ayuso, P., Agúndez, J.A.G., Pajares, M.A., Pérez-Sala, D. (2013) Inflamm. Allergy Drug Targets 12, 162-171. PMID: 23596995
Acute liver injury induces nucleocytoplasmic redistribution of hepatic methionine metabolism enzymes. Delgado, M., Garrido, F., Pérez-Miguelsanz, J., Pacheco, M., Partearroyo, T., Pérez-Sala, D., Pajares, M.A. (2014) Antioxid. Redox Signal. 20, 2541-2554. PMID: 24124652
Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism. Martínez-Vega, R., Garrido, F., Partearroyo, T., Cediel, R., Zeisel, S.H., Martínez-Álvarez, C., Varela-Moreiras, G., Varela-Nieto, I.*, Pajares, M.A.* (2015) FASEB J. 29, 418-432. PMID: 25384423
The oncogene PDRG1 is an interaction target of methionine adenosyltransferases. Pérez, C., Pérez-Zúñiga, F.J., Garrido, F., Reytor, E., Portillo, F., Pajares, M.A.* (2016) PLoS ONE 11, e0161672. PMID: 27548429
Betaine homocysteine S-methyltransferase emerges as a new player of the nuclear methionine cycle. Pérez-Miguelsanz, J., Vallecillo, N., Garrido, F., Reytor, E., Pérez-Sala, D., Pajares, M.A.* (2017) Biochim. Biophys. Acta- Mol. Cell Res. 1864, 1165-1182. PMID: 28288879