Molecular and Translational Pharmacology
Blegdamsvej 3, 2200 KÃ¸benhavn N., 18 Bygning 18, Bygning: 18-5-42
In the Mathiasen lab (group site) we focus on investigating the signaling properties and unexplored biology of Adhesion G protein-coupled receptor (GPCRs) and the implications of this receptor family in human health and disease.
Adhesion GPCRs are crucial regulators of diverse functions in the nervous, musculoskeletal, cardiac and immune systems, and their dysregulation has been linked to a variety of diseases and cancers. In the lab we have a special focus on the adhesion GPCR ADGRL3 (historically latrophilin 3 or LPHN3). Human genetics has associated ADGRL3 with increased risk of attention deficit hyperactivity disorder (ADHD) and substance abuse, and knockdown in multiple animal species (fly, fish, mouse and rat) leads to hyperlocomotion and altered dopamine signaling. Thus, ADGRL3 may constitute a potential novel target for treatment of neuropsychiatric disorders that involve dopamine dysfunction, such as schizophrenia.
ADGRL3 compose a giant protein structure that combines several functions. On the one hand, it can bridge between neurons to stabilize the synapse by binding extracellular transsynaptic protein ligands, and on the other hand, it can control intracellular signaling cascades through its transmembrane GPCR domain. In the lab we are interested in mapping ADGRL3's basic biological functions such as how the receptor is activated, what downstream signaling cascades are turned on as a consequence of activation as well as what cellular response ADGRL3 activation leads to.
Recent advances in the field suggest that adhesion GPCR intracellular signaling and extracellular adhesive interactions might be functionally integrated through mechanical stress. In the lab we aim to develop molecular scale tools to study the impact of mechanical stress across ADGRL3 in response to synaptic ligand interactions. To do so we combine a suite of molecular biology techniques and advanced GPCR signaling assays with the development of novel single molecule microscopy approaches.