Research projectsOur research interests revolve around the validation of emerging biological targets with therapeutic or diagnostic potential. More specifically, the lab is interested in following targets:
- Exploration of GPCRs chemical space
- Novel molecular transporters for cell penetration
- Inhibitors of type 2 transmembrane serine proteases (TTSPs)
- Emerging class of antibiotics
G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and the target of about 40% of drugs. In this family, our research work focuses on the design of ligands capable to bias peptidergic receptors signaling such as APJ (apelin hormone target) and NTS1 (neurotensin hormone target) receptors. Biased signaling is a relatively new concept, which aims to favor specific signaling pathways. Conceptually, this would allow to bias signaling pathways toward the desired effects at the expense of signaling pathways leading to adverse effects by modulating ligand structure. We are also interested in receptors activated by fatty acids such as GPR40 and GPR120, in a polypharmacology context against type 2 diabetes
Macrocycles are a unique chemical class which combine the ability to display distant pharmacophores while keeping a semi-rigid structure. Therefore, they have the potential to combine the benefits of large molecules in terms of structural information content and the benefits of small molecules in term of PK-ADME. Several projects involving macrocycles are ongoing, with the goal to inhibit protein-protein interactions and modulate GPCRs signalisation.
We develop new molecular transporters capable to help impermeable molecules cross cell membranes. In the long term, we target the development of vectors capable to discriminate different cellular types for targeted drug delivery.
In this class of protein, we focus on matriptase and matriptase 2. We have designd a new class of peptidomimetic inhibitors that display efficacy to inhibit the replication of the H1N1.
Riboswitches are secondary RNA structures that controle a specific genetic operon. Inhibiton of certain riboswitches is emerging as a promising target against multiresistant pathogens such as methycillin resistant Staphylococcus aureus (MRSA) or Clostridium difficile. Our group also is interested in teixobactin. Discovered in 2015, teixobactin is a macrocyclic depsipeptide that possesses antibacterial activity in Gram positive bacteria, including the most resistant. There is no strain of bacteria that developped a known resistance to this antibiotic so far. A Trojan horse-like strategy would likely allow teixobactin to have activity against Gram-negative bacteria.
Our working environment is highly multidisciplinary. Our network of collaborators includes groups of R. Leduc, M. Grandbois, E. Escher, J.B. Denault (Pharmacology); P. Sarret (Physiology), D. Lafontaine, F. Malouin (Biology); L.C. Fortier (Microbiology); R. Najmanovich, P. Lavigne (Biochemistry), M. Richter, A. de Brum-Fernandes (Medecine), M. Lepage, B. Guérin (Radiobiology), M. Bouvier (IRIC, Montreal), V. Poitout (Centre de Recherche sur le Diabète de Montréal), A. Yudin (U. Toronto), Bruno Reversade (Singapour).
We are grateful to the following funding agencies :