A5029100534- Receptor Mechanisms and Signaling
- Photochromic and Fluorescence Chemistry
- Photoreceptor and optogenetics research
- Neuropeptides and Animal Physiology
- Biochemical Analysis and Sensing Techniques
- Cellular transport and secretion
- melanin and skin pigmentation
- Neuroscience and Neuropharmacology Research
- Luminescence and Fluorescent Materials
- Retinal Development and Disorders
- Protein Kinase Regulation and GTPase Signaling
Cornell University
2018-2022
Weill Cornell Medicine
2018-2022
University of Pennsylvania
2015-2016
Children's Hospital of Philadelphia
2015-2016
Penn Center for AIDS Research
2015
Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of factors to their sites origin. Melanosomes other lysosome-related organelles obtain cargoes from early endosomes, but the machinery involved its pathway are unknown. Here, we show that v-SNARE VAMP7 mediates melanosomes tubular carriers also carry protein TYRP1 require BLOC-1 for formation. Using live-cell imaging, identify a employs distinct carriers. The harbor...
Hermansky–Pudlak syndrome (HPS) is a group of disorders characterized by the malformation lysosome-related organelles, such as pigment cell melanosomes. Three nine HPS subtypes result from mutations in subunits BLOC-2, protein complex with no known molecular function. In this paper, we exploit melanocytes mouse models to place BLOC-2 within cargo transport pathway recycling endosomal domains maturing BLOC-2–deficient melanocytes, melanosomal TYRP1 was largely depleted granules and underwent...
G protein-coupled receptors (GPCRs) interact with intracellular transducers to control both signal initiation and desensitization, but the distinct mechanisms that regulation of different GPCR subtypes are unclear. Here we use fluorescence imaging electrophysiology examine metabotropic glutamate receptor (mGluR) family. We find properties across in rapid desensitization internalization, striking differences between group II mGluRs. mGluR3, not mGluR2, undergoes glutamate-dependent...
G protein-coupled receptors (GPCRs) mediate the transduction of extracellular signals into complex intracellular responses. Despite their ubiquitous roles in physiological processes and as drug targets for a wide range disorders, precise mechanisms GPCR function at molecular, cellular, systems levels remain partially understood. To dissect individual receptor subtypes with high spatiotemporal precision, various optogenetic photopharmacological approaches have been reported that use power...
Numerous processes contribute to the regulation of G protein-coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on seconds time scale or regulate cross-talk between receptors. Here, we reveal ability some GPCR kinases (GRKs) bind Gαq both drives acute desensitization and regulates functional interactions GPCRs. GRK2/3-mediated occurs within seconds, rapidly reversible, can occur upon local, subcellular activation. This kinase independent,...
Abstract The limitations of classical, soluble drugs in terms subtype-specificity, spatiotemporal precision, and genetic targeting have spurred the development advanced pharmacological techniques, including use covalently-tethered photoswitchable ligands. However, a major shortcoming tethered photopharmacology is inability to obtain optical control with comparable efficacy native ligand. To overcome photoisomerization efficiency ligand affinity, we developed family branched compounds target...