Group Leader/s

 

intro

 

 

Proteins are effectors of most physiological functions in cells and they play a key role in the extracellular medium. Protein function is finely tuned at multiple levels including synthesis and degradation, intracellular localization and posttranslational modifications. The posttranslational modification of proteins is a key mechanism for the regulation of their biological activity. Various biological mediators, including lipids and reactive oxygen and nitrogen species, as well as some drugs and toxins, can modify proteins posttranslationally. We are interested in the study of the importance of these processes in molecular pathophysiology and in the mechanisms of drug action. Our work includes several aspects: the structural and functional characterization of novel types of posttranslational modifications, the identification of novel protein targets for modification and the study of the pathophysiological consequences of these phenomena.

Protein lipoxidation is the posttranslational modification of proteins by oxidized reactive lipids. This is a process with ample implications in physiology and pathophysiology, as illustrated in the figure below. We are exploring novel aspects of this modification.

Intermediate filament proteins of the type III family, including vimentin and GFAP, play key roles in cell dynamics, homeostasis and cytoskeletal cross-talk. We have identified these proteins as targets for modifications by electrophilic lipids and oxidants, preferentially at their single cysteine residue. This has led to define their role as redox and stress sensors. Moreover, we are delineating novel roles for these proteins in essential cellular processes, like the interaction of vimentin with actin in cell division, and elucidating their involvement in disease.

Modification of proteins by drugs or their metabolites, a process know as haptenation, can contribute to adverse reactions, including drug allergy. We are studying protein haptenation by several drugs in the context of a National network on "Asthma, adverse reactions and allergy".

Video:PPM%20Lab%20CIB-CSIC%20DPerez-Sala2018.wmv

Redox Biology Special Issue on Lipoxidation targets

Lipoxidation targets

 
 

Funding

"The astrocyte nanofilament system in Alexander disease – from molecules to function, uncovering new leads for therapy” EJPRD2019-256 “ALEXANDER”. European Joint Program on Rare Diseases

“Validation of vimentin as a co-receptor for SARS-CoV-2 and intervention strategies”. CSIC PTI Global Health (PIE 202020E223/CSIC-COVID-19-100)

EU Project 675132 (H2020-MSCA-ITN-2015). Innovative Training Network. "MASS Spectrometry TRaining network for Protein Lipid adduct Analysis". MASSTRPLAN. Oct 2015-Sept 2019.

http://www.masstrplan.org/

"Proteoforms in pathophysiology and drug action: focus on intermediate filament proteins and selected drug targets" Ministerio de Ciencia e Innovación RTI-2018-097624-B-I00 (cofunded FEDER).

"Protein modification by lipoxidation and drug addition: novel perspectives for exploring disease mechanisms and therapeutic strategies" MINECO SAF2015-68590-R (cofunded FEDER).

Network for the Research on Asthma, Adverse and Allergic Reactions (ARADyAL). Instituto de Salud Carlos III. RETIC RD16/0006/0021.

COST Action CA19105 EpiLipidNET "Pan-European Network in Lipidomics and Epilipidomics"

COST Action CA15214 EUROCELLNET "An integrative action for multidisciplinary studies on cellular structural networks"

http://www.cost.eu/COST_Actions/ca/CA15214

 

More info

Networking:

Synthetic Cell Initiative https://www.syntheticcell.eu/

Former networks

COST Action CM1001 "Chemistry of non-enzymatic protein modification: modulation of protein structure and function"

COST: Action TD1304 Zinc-Net: the Network for the Biology of Zinc

- Red de Reacciones Adversas a Alergenos y Fármacos (RIRAAF) RETIC ISCIII. RD12/0013/0008

Patent applications:

- "Protein tag for endo-lysosomal localization and degradation". D. Pérez-Sala, P. Boya, K, Stamatakis. P200802721. September 25, 2008.

- "Compounds with 2-cyclopentenone structure as inhibitors of AKR family enzymes". D. Pérez-Sala, B. Díez. P201030449. March 25, 2010.

- “Use of 5-carboxymethyl-3-mercapto-1,2,4-triazino-[5,6-b]indoles and their pharmaceutical composition” Milan Stefek, Ivana Milackova, Beatriz Díez Dacal, Dolores Pérez-Sala Gozalo, Marta Soltesova-Prnova. WO2015/057175 A, 23-4-2015.