After some years of academic formation (I studied Pharmacy and a Master degree on Neuroscience from the University of Barcelona obtained in 2012) I was lucky to join the Neuropharmacology and Pain research lab in September 2012, where I started the Ph.D. training with a FPI Grant (Formación de Personal Investigador) from the Ministry of Economy and Competitiveness, under the supervision of Dr. Francisco Ciruela and Dr. Víctor Fernández-Dueñas.
During this period my work was focused on deciphering the role of the Parkinson related GPR37, also known as PAEL receptor in the Central Nervous System, and looking for specific ligands for this orphan receptor. As GPR37 was an orphan receptor (which means that does not exist any ligand described that binds specifically to this receptor) we had to start building the house from the base. We produced recombinant proteins, specific antibodies and all the tools required to study this interesting and mysterious receptor implicated in the Parkinson’s neuropathological hallmarks. We also studied the interaction of this receptor with adenosine, dopamine and glutamate in different brain regions of interest such as striatum to find new potential treatments for Parkinson’s disease, and finally we focused on studying the potential use of the GPR37 as a biomarker in Parkinson’s disease (using both CSF and serum). We generated a homemade ELISA assay to detect GPR37 peptides in body fluids.
As a result from all this work, I have participated in very different research projects, published more than 18 papers in peer-reviewed international journals and defend my work on international congress. Since 2018, I’ve been also collaborating with Laboratorios Dr. Esteve designing a new biosensor to facilitate Sigma1 receptor ligands screenings, a receptor implicated in different diseases, such as cocaine addiction, amnesia, pain, depression or Alzheimer’s disease.
Research Interest: At this moment my research is focused in desciphering the role of different GPCRs in neurodegenerative diseases such as Parkinson’s disease, Alzheimer disease and Amyotrophic Lateral Sclerosis and Multiple Sclerosis.
Grants: FPI grant, Eurolife Postdoctoral Mobility and Knowledge exchange
URL: https://www.linkedin.com/in/xaviermoratoarus/
List of Publications:
1. Morató X; Rodrigo Antunes Cunha; Francisco Ciruela. GPR37 emerges as an important modulator of adenosinergic transmission in the striatum. Neural Regeneration Research. 2019.
2. Morató X; Francisco Q Gonçalves; Joao Pedro Lopes; Olga Jauregui; Concepció Soler; Victor Fernández-Dueñas; Rodrigo Antunes Cunha; Francisco Ciruela. Chronic adenosine A2A receptor blockade induces locomotor sensitization and potentiates striatal LTD in GPR37 deficient mice. J Neurochem. 2019 Mar;148(6):796-809. doi: 10.1111/jnc.14653. Epub 2019 Jan 28.
3. Luján R, Aguado C, Ciruela F, Arus XM, Martín-Belmonte A, Alfaro-Ruiz R, Martínez-Gómez J, de la Ossa L, Watanabe M, Adelman JP, Shigemoto R, Fukazawa Y. SK2 Channels Associate With mGlu1α Receptors and CaV2.1 Channels in Purkinje Cells. Front Cell Neurosci. 2018 Sep 19;12:311. doi: 10.3389/fncel.2018.00311. eCollection 2018.
4. Gómez-Soler M, Cordobilla B, Morató X, Fernández-Dueñas V, Domingo JC, Ciruela F. Triglyceride Form of Docosahexaenoic Acid Mediates Neuroprotection in Experimental Parkinsonism. Front Neurosci. 2018 Aug 28;12:604. doi: 10.3389/fnins.2018.00604. eCollection 2018.
5. Morató X, Luján R, Gonçalves N, Watanabe M, Altafaj X, Carvalho AL, Fernández-Dueñas V, Cunha RA, Ciruela F. Metabotropic glutamate type 5 receptor requires contactin-associated protein 1 to control memory formation. Hum Mol Genet. 2018 Oct 15;27(20):3528-3541. doi: 10.1093/hmg/ddy264.
6. Eduard Tolosa; Teresa Botta-Orfila; Morató X; Calatayud C; Ferrer-Lorente R; Martí MJ; Fernández M; Gaig C; Raya Á; Consiglio A; Mario Ezquerra; Rubén Fernández Santiago. MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients. Neurobiology of Aging. 5 - 32, pp. 283 - 291. Peter R. Rapp, 20/09/2018. ISSN 0197-4580.
7. Morató X, Luján R, López-Cano M, Gandía J, Stagljar I, Watanabe M, Cunha RA, Fernández-Dueñas V, Ciruela F. The Parkinson's disease-associated GPR37 receptor interacts with striatal adenosine A2A receptor controlling its cell surface expression and function in vivo. Sci Rep. 2017 Aug 25; 7(1):9452.
8. Kate Sokolina1#, Saranya Kittanakom1#, Jamie Snider, Max Kotlyar, Pascal Maurice, Jorge Gandía, Abla Benleulmi-Chaachoua, Kenjiro Tadagak, Victoria Wong, Ramy H. Malty, Viktor Deineko, Hiroyuki Aoki, Shahreen Amin, Laura Riley, Zhong Yao, Morató X, Sara Rahmati, Hiroyuki Kobayashi, Javier Menendez, Daniel Auerbach, Stephane Angers, Natasa Pržulj, Michel Bouvier, Mohan Babu, Francisco Ciruela, Ralf Jockers, Igor Jurisica, and Igor Stagljar. Systematic protein-protein interaction mapping for clinically-relevant human GPCRs. Molecular Systems Biology. 2017 Mar 15;13(3):918.
9. Morató X, Marc López, P. M. Canas, R. A. Cunha, Francisco Ciruela. Brain membrane fractionation: An ex vivo approach to assess sub-synaptic protein localization. Journal of Visualized Experiments. J Vis Exp, May 2017, 12 (123).
10. Paulo A. de Oliveira, James A.R. Dalton, Marc López-Cano, Adrià Ricarte, Morató X., Filipe C. Matheus, Andréia S. Cunha, Christa E. Müller, Reinaldo N. Takahashi, Víctor Fernández-Dueñas, Jesús Giraldo, Rui D. Prediger, Francisco Ciruela. Angiotensin II type 1/Adenosine A2A receptor oligomers: a novel target for tardive dyskinesia. Scientific reports. Sci Rep. 2017 May 12;7(1):1857.
11. Víctor Fernández-Dueñas, Jhonny Azuaje, Morató X., Begoña Cordobilla, Joan Carles Domingo, Eddy Sotelo, Francisco Ciruela. Synthesis and characterization of a new bivalent ligand based on the combination of caffeine and docosahexaenoic acid. Molecules. Feb 2017. 27;22(3).
12. Rial D, Morató X, Real JI, Gonçalves FQ, Stagljar I, Pereira FC, Fernández-Dueñas V, Cunha RA, Ciruela F. Parkinson's disease-associated GPR37 receptor regulates cocaine-mediated synaptic depression in corticostriatal synapses. Neurosci Lett. Jan 2017. 18;638:162-166. Page 6 of 7
13. Lopes JP1, Morató X1, Souza C, Pinhal C, Machado NJ, Canas PM, Silva HB, Stagljar I, Gandía J, Fernández-Dueñas V, Luján R, Cunha RA, Ciruela F. The role of parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system. J Neurochem. 2015 Jul; 134(1):135-46.
14. Gandía J, Morató X, Stagljar I, Fernández-Dueñas V, Ciruela F. Adenosine A2A receptor-mediated control of pilocarpine-induced tremulous jaw movements is Parkinson's disease-associated GPR37 receptor-dependent. Behav Brain Res. 2015 Jul 15; 288:103-6.
15. García-Negredo G, Soto D, Llorente J, Morató X, Galenkamp KM, Gómez-Soler M, Fernández-Dueñas V, Watanabe M, Adelman JP, Shigemoto R, Fukazawa Y, Luján R, Ciruela F. Coassembly and coupling of SK2 channels and mGlu5 receptors. J Neurosci. 2014 Oct 29;34(44):14793-802.
16. Botta-Orfila T, Morató X, Compta Y, Lozano JJ, Falgàs N, Valldeoriola F, Pont-Sunyer C, Vilas D, Mengual L, Fernández M, Molinuevo JL, Antonell A, Martí MJ, Fernández-Santiago R, Ezquerra M. Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease. J Neurosci Res. 2014 Aug;92(8):1071-7. doi: 10.1002/jnr.23377. Epub 2014 Mar 20.
17. Fernández-Dueñas V, Gómez-Soler M, Morató X, Núñez F, Das A, Kumar TS, Jaumà S, Jacobson KA, Ciruela F. Dopamine D(2) receptor-mediated modulation of adenosine A(2A) receptor agonist binding within the A(2A)R/D(2)R oligomer framework. Neurochem Int. 2013 Jul;63(1):42-6.
18. Gandía J, Fernández-Dueñas V, Morató X, Caltabiano G, González-Muñiz R, Pardo L, Stagljar I, Ciruela F. The Parkinson's disease-associated GPR37 receptor-mediated cytotoxicity is controlled by its intracellular cysteine-rich domain. J Neurochem. 2013.
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