Icaro Ariel Simon

Current research

G-protein coupled receptors (GPCRs) are one of the largest protein superfamilies in the human genome, mediating extracellular to intracellular signaling responses and being crucial for nearly every physiological process. About one-third of all currently approved drugs target a GPCR, especially aminergic receptors such as histamine, dopamine and serotonin receptors.

Recent developments in GPCR pharmacology have shown that agonists can exhibit functional selectivity (biased agonism) by either activation of G-proteins or recruitment of β-arrestins, therefore triggering alternative downstream signaling pathways, one of them implicated in therapeutic effects while the other potentially responsible for a drug’s side effects.

My research project has a particular focus on serotonin (5-hydroxytryptamine; 5HT) subtype A receptor, or 5-HT2A, which is a validated drug target in the treatment of schizophrenia, cluster headaches, and glaucoma as well as the main target for hallucinogenic drugs of abuse such as LSD, DMT, and mescaline.

In this project, the functional selectivity mechanisms at 5-HT2A are being investigated by molecular modeling in order guide the design and synthesis of novel ligands for this serotonin receptor, aiming the development of safer drugs that elicit purely the therapeutically beneficial effects.

This Ph.D. project is a part of the European Ph.D. Training Network: Selective Agonists for the 5-HT2A Serotonin Receptor (SAFER). SAFER is funded by the EU Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 765657.

Further information about this project can be found on our website: http://www.safer-itn.eu/