E030 – Platelet Proteomics

Objectives

Our research focuses on the study of platelets and extracellular vesicles in those pathologies in which unwanted platelet activation is involved, such as obesity and coronary disease. This is done by a combination of proteomic and functional approaches. The goal is to investigate platelets at the molecular level to identify new biomarkers and drug targets that can help treat/diagnose atherothrombosis. Potential drug targets identified by proteomics are being investigated to find small molecules that can inhibit/modulate them.

Lines of research

The main lines of research are related to the search for platelet biomarkers and drug targets in obesity and cardiovascular disease. Platelets and extracellular vesicles are investigated. Antithrombotic drugs are sought against some of the identified targets. The main funding comes from the EU (ITN-European Joint Doctorate), the Ministry of Science and Innovation of Spain and the Spanish Society of Thrombosis and Haemostasis (SETH).

• María N. Barrachina, Irene Izquierdo, Lidia Hermida-Nogueira, Luis A. Morán, Amparo Pérez, Ana B. Arroyo, Nuria García-Barberá, Rocío González-Conejero, Sara Troitiño, Johannes A. Eble, José Rivera, Constantino Martínez, María I. Loza, Eduardo Domínguez and Ángel García. The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential. Int. J. Mol. Sci. 2021. 22(7), 3304. doi: doi.org/10.3390/ijms22073304
• Barrachina MN, Hermida-Nogueira L, Moran LA, Casas V, Hicks SM, Sueiro AM, Di Y, Andrews RK, Watson SP, Gardiner EE, Abian J, Carrascal M, Pardo M, García Á. Phosphoproteomic Analysis of Platelets in Severe Obesity Uncovers Platelet Reactivity and Signaling Pathways Alterations.  Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):478-490. doi: 10.1161/ATVBAHA.120.314485
• Hermida-Nogueira L, Barrachina MN, Morán LA, Bravo S, Diz P, García Á, Blanco J. Deciphering the secretome of leukocyte-platelet rich fibrin: towards a better understanding of its wound healing properties. Sci Rep. 2020 Sep 3;10(1):14571. doi: 10.1038/s41598-020-71419-7.PMID: 32884030 (link is external) Free PMC article
• Barrachina MN, Sueiro AM, Casas V, Izquierdo I, Hermida-Nogueira L, Guitián E, Casanueva FF, Abián J, Carrascal M, Pardo M, García Á. A Combination of Proteomic Approaches Identifies A Panel of Circulating Extracellular Vesicle Proteins Related to the Risk of Suffering Cardiovascular Disease in Obese Patients. Proteomics. 2019 Jan;19(1-2):e1800248. doi: 10.1002/pmic.201800248. Epub 2018 Dec 27.PMID: 30536591(link is external).
• Izquierdo I, Barrachina MN, Hermida-Nogueira L, Casas V, Morán LA, Lacerenza S, Pinto-Llorente R, Eble JA, de Los Ríos V, Domínguez E, Loza MI, Casal JI, Carrascal M, Abián J, García A. A Comprehensive Tyrosine Phosphoproteomic Analysis Reveals Novel Components of the Platelet CLEC-2 Signaling Cascade. Thromb Haemost. 2020 Feb;120(2):262-276. doi: 10.1055/s-0039-3400295. Epub 2020 Jan 4.PMID: 31901221(link is external).
• Izquierdo I, Barrachina MN, Hermida-Nogueira L, Casas V, Eble JA, Carrascal M, Abián J, García Á.  Platelet membrane lipid rafts protein composition varies following GPVI and CLEC-2 receptors activation.  J Proteomics. 2019 Mar 20;195:88-97.(link is external)
• María N. Barrachina, Aurelio M. Sueiro, Irene Izquierdo, Lidia Hermida-Nogueira, Esteban Guitián, Felipe F. Casanueva, Richard W. Farndale, Masaaki Moroi, Stephanie M. Jung, María Pardo, Ángel García. GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: Elucidating potential anti-atherothrombotic targets in obesity. Atherosclerosis Volume 281, February 2019, Pages 62-70. doi: 10.1016/j.atherosclerosis.2018.12.023
• Luis A Morán, Ying Di, Marcin A Sowa, Lidia Hermida-Nogueira, María N Barrachina, Eleyna Martin, Todd H Mize, Joanne C Clark, Johannes A Eble, David Moreira, Alice Y Pollitt, María I Loza, Eduardo Domínguez, Steve P Watson, Angel Garcia. Katacine is a new ligand of CLEC-2 that acts as a platelet agonist. Thrombosis and Haemostasis, in press. doi: 10.1055/a-1772-1069

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