Fredrik Leeb-Lundberg, Professor
One major aim of our research is to identify new avenues for drug development.
Communication between cells is necessary for the integration of all physiological events. Perturbation in this contact is responsible for many pathological events such as cancer, diabetes, and high blood pressure. Cell communication is based on the presentation of a chemical substance by one cell, which is then recognized by a receptor on the surface of a recipient cell.
G protein-coupled receptors (GPCR) constitute the largest family of receptors and represent the third largest family of genes in the human genome. They participate in almost all physiological events ranging from endocrine regulation, neurotransmission, and sensory perception.
Our research involves studies of the molecular mechanisms underlying ligand and drug recognition and transmembrane signaling by a GPCR and the regulation of these events. To do this, we use primarily receptors for kinins, which constitute a family of ubiquitous and exceedingly potent and efficacious proinflammatory vasodilator peptide agonists that are released in response to injury and trauma.
One question that is addressed with this system, which is fundamental to pharmacology and drug development, is the molecular basis for drug efficacy, i.e. the capacity of a drug to activate or inactivate a receptor response.
A second question is the role of various plasma membrane microdomains such as lipid rafts and clathrin-coated pits in receptor trafficking. We also study a novel GPCR for estrogen and the role of this receptor in vascular and metabolic integrity. Numerous vasodilator agonists tightly regulate the degree of blood vessel contractility and hence blood flow by regulating the level endothelial-derived NO.
A third question that we address is the nature of the interaction of GPCR with intracellular effectors such endothelial nitric oxide (NO) synthase.
GPCR are fundamental to pharmacology and have attracted a lot of attention in the pharmaceutical industry and the clinic since they are unsurpassed as targets for therapeutic drugs.