Sergi Ferré, Ph.D.
Molecular Targets and Medications Discovery Branch, Integrative Neurobiology Section
251 Bayview Boulevard
Suite 200, Room 07A707
Baltimore, MD 21224
We are interested in the role of receptor heteromers as targets for drug development in neuropsychiatric disorders and drug addiction. Receptor heteromers are higher order molecular entities that are the result of combinatorial evolution and endowed with unique biochemical and functional properties that could be harnessed for therapeutic purposes. Receptor heteromers uncover a previously unforeseen vast number of new possible subpopulations of G-protein-coupled receptor subtypes, with specific neuronal localizations and functions. Their potential ligand selectivity implies that receptor heteromers constitute potential new targets for drug development.
Our research deals preferentially with the discovery of heteromers of receptors that are targets for addictive drugs or that are localized in brain circuits that are involved in addictive behaviors (such as dopamine, glutamate, cannabinoid and adenosine receptors) and with the analysis of their biochemical and pharmacological properties involving studies at the cellular level as well as at the in vivo level.
At the cellular level, mammalian cell lines transfected with the receptors under study are used to demonstrate receptor heteromerization by protein-protein interaction experiments. We then look for the unique biochemical properties of the receptor heteromer, which can be used as a “biochemical fingerprint” for its identification in the brain. In vivo models are established for the evaluation of the functional significance of receptor heteromers, which include intracranial electrical stimulation, in vivo microdialysis and functional magnetic resonance imaging. The cellular and in vivo models complement each other and are then used to find receptor heteromer-selective drugs.
Belcher AM, Volkow ND, Moeller FG, Ferré S. Personality traits and vulnerability or resilience to substance use disorders. Trends Cogn Sci. 2014;18(4):211-7.
Bonaventura J, Quiroz C, Cai NS, Rubinstein M, Tanda G, Ferré S. Key role of the dopamine D<sub>4</sub> receptor in the modulation of corticostriatal glutamatergic neurotransmission. Sci Adv. 2017;3(1):e1601631.
Ferré S, Casadó V, Devi LA, Filizola M, Jockers R, Lohse MJ, Milligan G, Pin JP, Guitart X. G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol Rev. 2014;66(2):413-34.
Ferré S. The GPCR heterotetramer: challenging classical pharmacology. Trends Pharmacol Sci. 2015;36(3):145-52.
Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KD, Pin JP, Volkow ND, Waldhoer M, Woods AS, Franco R. Building a new conceptual framework for receptor heteromers. Nat Chem Biol. 2009;5(3):131-4.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on August 24th, 2017