Research Interest

The research conducted in our group is mainly focused on seeking new pharmacological strategies to reach an effective management of neurological, neuropsychiatric and pain diseases. Our aim consists of providing a deep mechanistic understanding of neurotransmitter receptors functioning which may help to design combined therapies or oligomer-tailored drugs in the near future. In addition, our interests include the development and implementation of novel biotechnological methodologies (e.g. fluorescence based biosensors, photopharmacology, etc.) that may eventually evolve into new tools for both the study and diagnostic of diseases.

Finally, our main goal is the translation of our results from the bench to the bedside and to clinical practice. Accordingly, to translate basic scientific findings into therapeutic interventions for patients we are also involved in clinical pharmacology studies, specially pharmacoepidemiological studies and clinical trials.

Technologies & Methods

• Molecular and in cell studies: Drug design, GPCR structure-acticity relationship, BRET, FRET, TR-FRET, biosensors, real-time single cell FRET, NanoBRET, fluorescent ligands, photopharmacology, primary neuronal cultures and brain slices, electrophysiology
• In animal studies: Pharmacological and genetic animal models for neurological diseases and pain (i.e. Parkinson disease, Alzheimer disease, schizophrenia and Pain). Knock-out animals for GPCRs
• In human studies: Peripheral and central biomarkers for neurological diseases, epidemiological studies

Active Projects

• • Cannabinoid actions in the diseased brain. (Iberoamerican Cannabinoid Research Network). Unión Iberoamericana de Universidades. UCM-02-2019. Ester Aso

• • Contracte del Programa Ramon y Cajal 2019. Ministerio de Economia y Competitividad. RYC-2019-027371-I. Francisco Ciruela

• • Descifrando las acciones farmacologías de la ketamina en los receptores de opioides. Ministerio de Ciencia e Innovación. PID2020-117989RA-I00. Jordi Bonaventura.

• • Dinámica de los agregados macromoleculares de heteroreceptores de dopamina-adenosina en esquizofrenia y trastornos neurodegenerativos. Ministerio de Ciencia e Innovación. PID2020-118511RB-I00. Francisco Ciruela.

• • Ecto-GPR37: a potential biomarker for Parkinson’s disease. Michael J. Fox Foundation for Parkinson’s Research. MJFF001051. Francisco Ciruela.

• • El complejo trans-sináptico formado por CB1-A2A y mGlu5 en el hipocampo como sustrato de los efectos terapéuticos de los cannabinoides en la enfermedad de Alzheimer. Ministerio de Ciencia, Innovación y Universidades. RTI2018- 097773-AI00. Ester Aso.

• • Neurofarmacologia i dolor. Agència de Gestió d’Ajuts Universitaris i de Recerca. 2017SGR1604. Francisco Ciruela.

• • Subvencions per a la formació de científics i tecnòlegs: modalitat personal investigador en formació (PIF-Salut) – PERIS – Departament de Salut. Departament de Salut de la Generalitat de Catalunya. SLT017/20/000114. Francisco Ciruela.

• • Vulnerabilidad a los efectos psicóticos del THC durante la adolescencia: implicación de la interacción entre los receptores CB1, A2A y D2. Ministerio de Sanidad, Servicios Sociales e Igualdad. 2020I041. Ester Aso.

• • 1 Confidential agreement.

Selected Publications

• • Alonso-Gardón, M., Elorza-Vidal, X., Castellanos, A., La Sala, G., Armand-Ugon, M., Gilbert, A., Di Pietro, C., Pla-Casillanis, A., Ciruela, F., Gasull, X., Nunes, V., Martínez, A., Schulte, U., CohenSalmon, M., Marazziti, D., & Estévez, R. (2021). Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic
    leukoencephalopathy proteins. Human Molecular Genetics, 30(17), 1649–1665. https://doi.org/10.1093/hmg/ddab155

• • Belluardo, N., Mudò, G., Di Liberto, V., Frinchi, M., Condorelli, D. F., Traversa, U., Ciruela, F., Ciccarelli, R., Di Iorio, P., & Giuliani, P. (2021). Investigating the Role of Guanosine on Human
    Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms. Frontiers in Pharmacology, 12, 658806. https://doi.org/10.3389/fphar.2021.658806

• • Bonaventura, J., Lam, S., Carlton, M., Boehm, M. A., Gomez, J. L., Solís, O., Sánchez-Soto, M., Morris, P. J., Fredriksson, I., Thomas, C. J., Sibley, D. R., Shaham, Y., Zarate, C. A., & Michaelides, M. (2021). Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability. Molecular Psychiatry, 26(11), 6704–6722. https://doi.org/10.1038/s41380-021-01093-2

• • Casadó-Anguera, V., Moreno, E., Sánchez-Soto, M., Cai, N. S., Bonaventura, J., Homar-Ruano, P., Rubinstein, M., Cortés, A., Canela, E. I., Ferré, S., & Casadó, V. (2021). Heteromerization between α2A adrenoceptors and different polymorphic variants of the dopamine D4 receptor determines pharmacological and functional differences. Implications for impulsive-control disorders. Pharmacological Research, 170, 105745. https://doi.org/10.1016/j.phrs.2021.105745

• • Godoy-Marín, H., Duroux, R., Jacobson, K. A., Soler, C., Colino-Lage, H., Jiménez-Sábado, V., Montiel, J., HoveMadsen, L., & Ciruela, F. (2021). Adenosine A2A Receptors Are Upregulated in Peripheral Blood Mononuclear Cells from Atrial Fibrillation Patients. International Journal of Molecular Sciences, 22(7), 3467. https://doi.org/10.3390/ijms22073467

• • Gomez, J. L., Bonaventura, J., Keighron, J., Wright, K. M., Marable, D. L., Rodriguez, L. A., Lam, S., Carlton, M. L., Ellis, R. J., Jordan, C. J., Bi, G. H., Solis, O., Pignatelli, M., Bannon,
    M. J., Xi, Z. X., Tanda, G., & Michaelides, M. (2021). Synaptic Zn2+ potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior. Translational Psychiatry, 11(1), 570. https://doi.org/10.1038/s41398-021-01693-0

• • Hu, F., Morris, P. J., Bonaventura, J., Fan, H., Mathews, W. B., Holt, D. P., Lam, S., Boehm, M., Dannals, R. F., Pomper, M. G., Michaelides, M., & Horti, A. G. (2021). 18F-labeled radiotracers
    for in vivo imaging of DREADD with positron emission tomography. European Journal of Medicinal Chemistry, 213, 113047. https://doi.org/10.1016/j.ejmech.2020.113047

• • Hüll, K., Fernández-Dueñas, V., Schönberger, M., LópezCano, M., Trauner, D., & Ciruela, F. (2021). Optical Control of Adenosine-Mediated Pain Modulation. Bioconjugate Chemistry, 32(9), 1979–1983. https://doi.org/10.1021/acs.bioconjchem.1c00387

• • López-Cano, M., Filgaira, I., Nolen, E. G., Cabré, G., Hernando, J., Tosh, D. K., Jacobson, K. A., Soler, C., & Ciruela, F. (2021). Optical control of adenosine A3 receptor function in psoriasis. Pharmacological Research, 170, 105731. https://doi.org/10.1016/j.phrs.2021.105731

• • López-Cano, M., Font, J., Aso, E., Sahlholm, K., Cabré, G., Giraldo, J., De Koninck, Y., Hernando, J., Llebaria, A., FernándezDueñas, V., & Ciruela, F. (n.d.). Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects. British Journal of Pharmacology, n/a(n/a). https://doi.org/10.1111/bph.15645

• • Morató, X., Garcia-Esparcia, P., Argerich, J., Llorens, F., Zerr, I., Paslawski, W., Borràs, E., Sabidó, E., Petäjä-Repo, U. E., Fernández-Dueñas, V., Ferrer, I., Svenningsson, P., & Ciruela, F. (2021). Ecto-GPR37: a potential biomarker for Parkinson’s disease. Translational Neurodegeneration, 10(1), 8. https://doi.org/10.1186/s40035-021-00232-7

• • Yarur, H. E., Zegers, J., Vega-Quiroga, I., Novoa, J., Ciruela, F., Andres, M. E., & Gysling, K. (2021). Functional Interplay of Type2 Corticotrophin Releasing Factor and Dopamine Receptors in the Basolateral Amygdala-Medial Prefrontal Cortex Circuitry. The International Journal of Neuropsychopharmacology, 24(3), 221–228. https://doi.org/10.1093/ijnp/pyaa079

• • Valle-León, M., Callado, L. F., Aso, E., Cajiao-Manrique, M. M., Sahlholm, K., López-Cano, M., Soler, C., Altafaj, X., Watanabe, M., Ferré, S., Fernández-Dueñas, V., Menchón, J. M., & Ciruela, F. (2021). Decreased striatal adenosine A2Adopamine D2 receptor heteromerization in schizophrenia. Neuropsychopharmacology, 46(3), 665–672. https://doi.org/10.1038/s41386-020-00872-9