Rafael Maldonado

 

Group website

Research Outline

We aim at identifying new therapeutical targets at the nervous system level. Our research focuses mainly on the neurobiological substrate of chronic pain, addictive processes, and cognitive disorders, including the links between brain and gut microbiota. We use multidisciplinary strategies, including novel behavioral techniques developed in our laboratory, associated with neurochemical, electrophysiological, genomic, and proteomic approaches. We complement our animal research with collaborative studies with clinical partners to evaluate the therapeutic approaches proposed in our studies in clinical trials (some already ongoing) and corroborate our animal studies' genomic and mechanistic results with findings in patients.

Research Lines

  • Identification of the key neurobiological mechanisms underlying addictive processes induced by palatable food.

  • Revealing the specific involvement of several receptors (CB1R, mu opioid receptor in GABA neurons, among others) in particular aspects of drug addiction. 

  • Studying the therapeutic interest of CB1R for chronic endometrial pain treatment.

  • Studying the therapeutic interest of CB2R, sigma receptor and specific subpopulations of opioid receptors for the management of neuropathic pain.

  • Identification of the  microbiota profiles associated to memory and obesity through particular metabolic routes and metabolomic profiles.

  • Identification of the sexual dimorphism in microbiota involved in obesity and menopausal status.

  • Understanding the complexity of the cognitive processes, including the role of peripheral CB1R, the protein kinase C signalling, and monoaminergic system.

  • Studying the potential therapeutic interest of the Ephrin-B2 protein and the vagus nerve stimulation for cognitive alterations.

 

Team during 2019-20

PhD students: Rocío Saravia Santos, Miriam Martínez Navarro, Sami Kummer, Ángela Ramírez López, Alejandra Escudero Lara, Lorena Galera López, Sheila Piedra Barrull, Ana Mª Gallego Román, Anna Vázquez Oliver, Eric Senabre Marchán, Pablo Calvé Pérez, Cecilia-Teresa Brambilla Pisoni, Pilar Ortiz Teba, Alejandra García Blanco, Araceli Bergadà Martínez, Andrea Rodríguez López, Maria del Mar Caijao, Violeta Jorge Pedraza, Lucía de los Reyes Ramírez, Solveiga Samulenaité

 

Postdocs: Beltrán Álvarez Pérez, Antonio Ortega Álvaro, María Sanchís Ollé, Mireia Carcolé Estrada, Sara Martínez Torres, Laura Domingo Rodríguez, Juan Antonio Ortega Sánchez

 

Technicians: Raquel Martín García, Dulce Real Muñoz, Marta Linares López, Francisco Porrón López, Jolita Jancyte, Neus Morgui Valls, Clara Seira Oriach, Alba Calvet Pavón

 

Other PI: Andrés Ozaita Mintegui

 

Senior scientists: Elena Martín García, Miquel Martín Sánchez


Project managers: Miquel Àngel Serra Beltrán,  Olga Millán Portillo

 

Selected publications

1. Escudero-Lara A, Argerich J, Cabañero D, Maldonado R (2020). Disease modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain. eLife, 9: e50356. http://www.doi.org/10.7554/eLife.50356. PMID: 31931958.

 

2. Domingo-Rodríguez L, Ruiz de Azua I, Dominguez E, Sanabre E, Serra I, Kummer S, Navandar M, Baddenhausen S, Hoffmann C, Andero R, Gerber S, Navarrete M, Dierssen M, Lutz B, Martín-García E, Maldonado R (2020). A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nature Communications, 11:1-13. http://www.doi.org/10.1038/s41467-020-14458-y. PMID: 32034128

 

3. Cabañero D, Ramírez-López A, Drews E, Schmöle A, Otte DM, Wawrzczak-Bargiela A, Huerga Encabo H, Kummer S, Ferrer-Montiel A, Przewlocki R, Zimmer A, Maldonado R (2020). Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropatic pain. eLife, 9: e55582. http://www.doi.org/10.7554/eLife.55582. PMID: 32687056.

 

4. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, Contresas-Rodríguez O, Blasco G, Coll C, Biarnñes C, Miranda-Olivos R, Latorre J, Moreno-Navarrete JM, Castells-Novau A, Sabater M, Palomo –Buitrago ME, Puig J, Pedraza S, Gich J, Pérez-Brocal V, Ricart W, Moya A, Fernández-Real X, Ramió-Torrentà L, Pamplona R, Sol J, Jové M, Portero-Otin M, Maldonado R, Fernández-Real JM (2020). Obesity impairs short-term and working memory through gut microbial metabolism of aromatic aminoacdis. Cell Metabolism, 32:1-13. http://www.doi.org/10.1016/j.cmet.2020.09.002. PMID: 33514598

 

5. - Navarro-Romero A, Vázquez-Oliver A, Gomis-González M, Garzón-Montesinos C, Falcón-Moya R, Pastor A, Martín-García E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodríguez-Moreno A, Maldonado R, Ozaita A (2019). Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome. Neurobiol Dis. 125:92-106. http://www.doi.org/10.1016/j.nbd.2019.01.014. PMID: 30685352

 

Other relevant information 

PATENT APPLICATIONS

 

Title: Use of (R)-9-(2-5-difluorophenethyl)-4-ethyl-2-methyl-1-oxa-4,9-diazaspiro [5.5]undecan-3-one for the treatment of nociceptive pain, neuropathic pain, osteoarthritis pain and cancer pain, while having reduced side effects compared to opioids.

Inventors: Begoña Fernández Pastor, Alba Vidal Torres, Mireia Carcolé Estrada, Rafael Maldonado López, José Miguel Vela Hernández, Manuel Merlos Roca, Daniel Zamanillo Castanedo.

Application number: 19382658.3-1112.

Application date / Priority date: 23/9/2019

Filing date: 31/7/2019

Publication number & date: pending

Holding entity: Esteve Pharmaceuticals, S.A.

 

Title: Peptide compounds for reducing side effects of CB1 receptor agonists

Inventors: Rafael Maldonado, David Andreu, Maria Gallo (UPF); Leonardo Pardo (UAB); Vicent Casadó, Estefania Moreno (UB); Miguel Castanho (IMM/Univ. Lisboa), Vera Neves, Marco Cavaco (IMM).

Application number: EP19382856.3

Application date / Priority date: 3/10/2019

Publication number & date: pending

International Application number: PCT/EP2020/077642

International Filing date: 02/10/2020

Publication number & date: pending

Holding entities: Universitat Pompeu Fabra (UPF), Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB) and Instituto de Medicina Molecular João Lobo Antunes -Faculdade de Medicina da Universidade de Lisboa (IMM-UL).

 

Title: Gut microbiota composition and uses thereof.

Inventors: José Manuel Fernández-Real; María Arnorriaga; Rafael Maldonado; Aurelius Burokas

Application number: EP20382592

Application date / Priority date: 01/07/2020

Publication number & date: pending

Holding entities: Institut d’Investigacions Biomèdiques de Girona (IDIBGI), Universitat Pompeu Fabra (UPF), Universitat de Valencia (UV), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) and Centro de Investigación Biomédica en Red (CIBER).

 

ORGANISATION OF CONFERENCES AND WORKSHOPS

 

- Rafael Maldonado and Andrés Ozaita. Scientific Organiser of the XX Annual Meeting of the Sociedad Española de Investigación en Cannabinoides, Barcelona, Spain (2019).

- Elena Martín. Scientific Organiser of the UAB Barcelona Summer School: Fundamentals of Psychobiology, Barcelona, Spain (2019).

- Andrés Ozaita. Scientific Organiser of the 2º Reunión de la Trisomy 21 Research Society, Barcelona (2019).

- Elena Martín. Scientific Organiser of the UAB Barcelona Summer School: How the brain works, Barcelona, Spain (2020). 

 

TECHNOLOGY TRANSFER – CONTRACTS WITH INDUSTRY

 

- Signing 9 research contracts with different pharmaceutical industries for a total value of 911.600€ in the period 2019-2020.

 

INVITATIONS AS KEYNOTE SPEAKER

 

- Rafael Maldonado. Conferencias en CosmoCaixa. Conferenciante invitado: “El efecto de las drogas en el cerebro”, Zaragoza, España, 22/1/2019.

- Rafael Maldonado. 1st International Workshop in Freiburg “Cannabinoids in the treatment of epilepsy”. Invited speaker: “Physiology of the endocannabinoid system”, Freiburg, Germany, 22/2/2019.

- Rafael Maldonado. I Jornada Internacional Socidrogalcohol. Invited speaker: “Neurobiology of food addiction”, Málaga, Spain, 5/3/2019.

- Rafael Maldonado. Conferencias del Ayuntamiento de L’Hospitalet de Llobregat. Conferenciante invitado: “Efectos del consumo de cannabis”, L’Hospitalet de Llobregat, España, 15/3/2019.

- Rafael Maldonado. Fórum de Recerca, Consorci d’Educació de Barcelona and Ajuntament de Barcelona, Hospital de la Santa Creu i Sant Pau. Conferenciante invitado: “Efectos del consumo de drogas: cómo investigarlo”, Barcelona, Spain, 25/3/2019.

- Fórum de Recerca, Consorci d’Educació de Barcelona and Ajuntament (City Hall) de Barcelona, Hospital de la Santa Creu i Sant Pau. Invited speaker: “Efectos del consumo de drogas: cómo investigarlo”, Barcelona, Spain, 25/3/2019. 

- Rafael Maldonado. Keynote lectures, Université Renée Descartes, Faculty of Medicine. Invited speaker: “Neurobiological bases of eating addictive-like behaviour”, Paris, France, 8/4/2019.

- Rafael Maldonado. Almirall MS Experts Summit. Invited speaker: “Cannabinoids and the endocannabinoid system”, Barcelona, Spain, 24-26/5/2019.

- Rafael Maldonado. Jornadas da Associação Portuguesa Adictologia “As vertigens do Risco e os Labirintos da Vontade. Olhares sobre Comportamentos Aditivos”. Conferenciante invitado: “Sistema endocannabinoide: efectos del cannabis en el cérebro”, Auditório da FCTUC Polo II, Coimbra, Portugal, 6/6/2019.

- Rafael Maldonado. III World congress & VI International congress on dual disorders in the context of neuroscience. Invited speaker: "Avances recientes para comprender las ventajas y los riesgos de la activación del sistema endocannabinoide", Madrid, Spain, 19-22/6/2019.

- Rafael Maldonado. European Pain Federation Krakow Pain School Krakow – Translational Pain Research: From Lab to Clinic. Conferenciante invitado: “Why opioids have less analgesic efficacy in neuropathic pain?”, Krakow, Poland, 22-27/6/2019.

- Andrés Ozaita. Gordon Research Conference on Cannabinoid Function in the CNS. Conferenciante invitado: “Impact of the peripheral endocannabinoid system in cognitive performance”, Casteldefells, Barcelona, Spain, 23/07/2019.

- Rafael Maldonado. Colloque ATHS Biarritz 2019, Colloque International "Addictions Toxicomanies Hépatites SIDA".  Conferenciante invitado: “Addiction à la nourriture: Implication du système endocannabinoïde dans les voies cortico-limbiques”, Biarritz, Francia, 3/10/2019.

- Rafael Maldonado. Seminario del Instituto de Neurociencias de Castilla y León, Universidad de Salamanca. Conferenciante invitado: "Involvement of the endocannabinoid system in food addiction”, Salamanca, España, 18/10/2019.

- Rafael Maldonado. Conferencia en la Reial Acadèmica de Medicina de la Comunitat Valenciana. Conferenciante invitado: “Efectos del consumo de cannabis”, València, España, 22/10/2019.

- Rafael Maldonado. Lisbon Addictions 2019 - 2nd European Conference on addictive behaviours and dependencies. Invited speaker: "The role of the endocannabinoid system in addiction", Lisbon, Portugal, 23/10/2019.

- Rafael Maldonado. II Congreso internacional sobre cánnabis y sus derivados: salud, educación y ley. Invited speaker: “Cannabis: mecanismo de acción y riesgos del consumo dependientes de la edad”, Catoira, Pontevedra, Spain, 8/11/2019.

- Rafael Maldonado. Conferencias en CosmoCaixa. Confereciante invitado: “Efectos de las drogas en el cerebro”, Lleida, España, 12/11/2019.

- Rafael Maldonado. Sinapsis’19 – VI Congreso Nacional de Patología Bio-Psicosocial. Confereciante invitado: “Efectos del cannabis en el cerebro”, Tenerife, España, 21/11/2019.

- Andrés Ozaita. 33rd European College of Neuropsychopharmacology (ECNP) Congress. Conferenciante invitado: “Cannabinoid type-1 receptor inhibition restores neurological phenotypes in a mouse model for Down syndrome”, Viena, Austria (Virtual), 14/09/2020.

- Andrés Ozaita. Webinar Semillero BIONEURO. Conferenciante invitado: “A propósito del cannabis”, Barranquilla, Colombia (Virtual), 22/09/2020.

- Andrés Ozaita. International course “Cannabis and Cannabinoids: chemistry, pharmacology and clinical applications”. Conferenciante invitado: “Mechanisms involved in the cognitive impairment induced by cannabinoids. Clues from animal models”. Montevideo, Uruguay (Virtual), 29/10/2020.

- Rafael Maldonado. Academia Nacional de Medicina de Francia. Conferenciante invitado: “Epigenetics of Nicotine Addiction”, 16/12/2020.