A5075926142- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- Neurobiology and Insect Physiology Research
- Axon Guidance and Neuronal Signaling
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Kruppel-like factors research
- melanin and skin pigmentation
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Nanofabrication and Lithography Techniques
- Lipid Membrane Structure and Behavior
Stanford University
2022-2025
Duke University
2015-2020
Duke University Hospital
2015-2019
Duke Medical Center
2015-2019
In the Wnt-β-catenin pathway, Wnt binding to Frizzled (Fzd) and LRP5 or LRP6 (LRP5/6) co-receptors inhibits degradation of transcriptional coactivator β-catenin by recruiting cytosolic effector Dishevelled (Dvl). Polymerization Dvl at plasma membrane recruits destruction complex, enabling phosphorylation LRP5/6, a key step in inhibiting degradation. Using purified Fzd proteins reconstituted lipid nanodiscs, we investigated factors that promote recruitment membrane. We found affinity for was...
Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled expressed in olfactory cilia membranes. Most show little to no cell surface expression nonolfactory cells due endoplasmic reticulum retention, which has slowed down biochemical studies. Here we provide evidence that structural instability divergence from conserved residues individual underlie intracellular retention using combination large-scale screening heterologous cells, point mutations, modeling,...
Deciphering how an odorant activates receptor (OR) and changes in specific OR residues affect its responsiveness are central to understanding our sense of smell. A joint approach combining site-directed mutagenesis functional assays with computational modeling has been used explore the signaling mechanics OR7D4. In this OR, a genetic polymorphism affects perception androstenone. Molecular simulations totaling 0.12 ms predicted that, similarly observations for other G-protein-coupled...
Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). In a sample of 2224 individuals 43 populations, we identified 45 single nucleotide polymorphisms. Coalescent modeling frequency-site-spectrum-based statistics significant deviation...
Wnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- tissue-specific manner. In the mammalian central nervous system, atypical ligand Norrin controls angiogenesis maintenance of blood-brain barrier blood-retina through pathway. Like Wnt, activates by binding heterodimerizing receptors Frizzled (Fzd) low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment intracellular transducer Dishevelled (Dvl)...
Wnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- tissue-specific manner. In the mammalian central nervous system, atypical ligand Norrin controls angiogenesis maintenance of blood-brain barrier blood-retina through pathway. Like Wnt, activates by binding heterodimerizing receptors Frizzled (Fzd) low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment intracellular transducer Dishevelled (Dvl)...
Many membrane proteins function as dimers or larger oligomers, including transporters, channels, certain signaling receptors, and adhesion molecules. In some cases, the interactions between individual may be weak and/or dependent on specific lipids, such that detergent solubilization used for biochemical structural studies disrupts functional oligomerization. Solubilized protein oligomers can captured in lipid nanodiscs, but this is an inefficient process produce stoichiometrically...
Abstract Deciphering how an odorant activates receptor (OR) and changes in specific OR residues affect its responsiveness are central to understanding our sense of smell. A joint approach combining site‐directed mutagenesis functional assays with computational modeling has been used explore the signaling mechanics OR7D4. In this OR, a genetic polymorphism affects perception androstenone. Molecular simulations totaling 0.12 ms predicted that, similarly observations for other G‐protein‐coupled...
Disulfide-linked bioconjugates allow the delivery of pharmacologically active or other cargo to specific tissues in a redox-sensitive fashion. However, an understanding kinetics, subcellular distribution, and mechanism disulfide cleavage such is generally lacking. Here, we report modular disulfide-linked TAMRA-BODIPY based FRET probe that can be readily synthesized, modified, conjugated cysteine-containing biomolecule enable real-time monitoring during receptor-mediated endocytosis cells. We...
Abstract Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled expressed in olfactory cilia membranes. Most show little to no cell surface expression non-olfactory cells due endoplasmic reticulum retention, which has slowed down biochemical studies. Here, we provide evidence that structural instability divergence from conserved residues individual underlie intracellular retention using combination large-scale screening heterologous cells, point mutations,...
Wnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- tissue-specific manner. In the mammalian central nervous system, atypical ligand Norrin controls angiogenesis maintenance of blood-brain barrier blood-retina through pathway. Like Wnt, activates by binding heterodimerizing receptors Frizzled (Fzd) Low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment intracellular transducer Dishevelled (Dvl)...
Wnt/ β -catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- tissue-specific manner. In the central nervous system, atypical ligand Norrin controls angiogenesis maintenance of blood-brain barrier blood-retina through pathway. Like Wnt, activates by binding heterodimerizing receptors Frizzled (Fzd) Low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment intracellular transducer Dishevelled (Dvl); this...
Wnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- tissue- specific manner. In the mammalian central nervous system, atypical ligand Norrin controls angiogenesis maintenance of blood-brain barrier blood-retina through pathway. Like Wnt, activates by binding heterodimerizing receptors Frizzled (Fzd) Low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment intracellular transducer Dishevelled (Dvl)...