Research in the Lab

Focal adhesions labeled with paxillin in wild type (WT) mouse embryonic fibroblasts (MEFs) or MEFs lacking both arrestin isoforms (double knockout; DKO). Note much larger size of the DKO MEFs.

Expression of GRK6-GFP (green) in medium spine neurons labeled with DARPP-32 (red) in the dopamine-depleted striatum of the rat (upper row). Lower row – expression of GRK6 in the cholinergic interneurons labeled with choline acetyltransferase (ChaT; red).

Lentiviral delivery of the GRK3 miRNA to the lesioned rat striatum. Upper panel – low magnification images labeled for GFP (green) expressed co-cistronically with the miRNA. Lower panel – expression of GFP in medium spine neurons co-labeled with the nuclear marker FOXP1 (red).

Lentiviraly delivered GRK3-GFP expressed in the lesioned rat striatum. Upper panel – low magnification images labeled for GFP (green). Lower panel – expression of GRK3-GFP in medium spiny neurons co-labeled with the nuclear marker FOXP1 (red).

Expression o fWT but not clathrin-binding deficient arrestins (ARR2-CBD or ARR3-CBD) in DKO MEFs rescues the cell size.

In a nutshell

The general direction of my lab is to elucidate the role abnormal signaling by G protein-coupled receptors (GPCR) plays in neurological and psychiatric disorders. We study signaling pathways in the brain regions involved in specific disorders using animal models and sophisticated molecular tools to manipulate signaling in vivo. My studies focus on the proteins involved in homologous desensitization of GPCRs, arrestins and G protein-coupled receptor kinases (GRKs). These are important regulatory proteins that determine critical parameters of the GPCR signaling. We combine molecular studies of GRKs and arrestins with experiments examining the role of these proteins in animal models of diseases in live animals using behavior as the readout. One project is designed to test the hypothesis that arrestin/GRK-mediated regulation of dopamine receptors plays a role in Parkinson’s disease and L-DOPA therapy. We use lentivirus-mediated gene transfer to overexpress wild type or mutant arrestins and GRKs or suppress their expression by microRNAs. The purpose of these experiments is to establish whether targeted modulation of receptor desensitization can adjust behavioral and molecular consequences of the dopamine depletion and L-DOPA therapy in a desired way. We are aiming at identifying GRK and arrestin isoforms as therapeutic targets for anti-dyskinesia therapy in PD. If you want to know more, please, read on.