A5060257534- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genetic and Kidney Cyst Diseases
- Synthesis and Characterization of Pyrroles
- Kruppel-like factors research
- Asymmetric Synthesis and Catalysis
- Multicomponent Synthesis of Heterocycles
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Carbohydrate Chemistry and Synthesis
- Cholesterol and Lipid Metabolism
- Receptor Mechanisms and Signaling
- Developmental Biology and Gene Regulation
- Genetic and rare skin diseases.
- Inflammasome and immune disorders
- Biofuel production and bioconversion
- Congenital Ear and Nasal Anomalies
- Neurotransmitter Receptor Influence on Behavior
- Alkaloids: synthesis and pharmacology
- Catalysis for Biomass Conversion
- Calcium signaling and nucleotide metabolism
- Stress Responses and Cortisol
- Ocular Disorders and Treatments
- Enzyme Catalysis and Immobilization
Stanford University
2012-2022
New Mexico Institute of Mining and Technology
2008-2012
Janssen (Italy)
1991
Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol not just but also sufficient to activate signaling by Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. influences Hh directly activating Smoothened (SMO), an orphan GPCR transmits signal across membrane all animals. Unlike GPCRs, which are regulated through their heptahelical transmembrane domains, SMO activated its extracellular cysteine-rich...
The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor GSDMD. is enteroinvasive bacterium causes hemorrhagic gastroenteritis in primates, but not rodents. contributes species specificity by ubiquitinating human, mouse, GSDMD and targeting it for...
Previously we proposed that transmission of the hedgehog signal across plasma membrane by Smoothened is triggered its interaction with cholesterol (Luchetti et al., 2016). But how cholesterol, an abundant lipid, regulated tightly enough to control a signaling system can cause birth defects and cancer? Using toxin-based sensors distinguish between distinct pools find activation Hedgehog are driven biochemically-defined, small fraction termed accessible cholesterol. Increasing accessibility...
Gα s protein–coupled receptors reduce the sensitivity of cells to morphogen Sonic Hedgehog.
Smoothened (SMO) transduces the Hedgehog (Hh) signal across plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one extracellular cysteine-rich domain (CRD) and a second transmembrane (TMD). How these sterol-binding sites mediate activation ligand Sonic (SHH) remains unknown. We find that mutations CRD (but not TMD) reduce fold increase activity triggered by SHH. SHH also promotes photocrosslinking of sterol analog intact cells. In contrast, binding TMD...
A long-standing mystery in vertebrate Hedgehog signaling is how Patched 1 (PTCH1), the receptor for ligands, inhibits activity of Smoothened, protein that transmits signal across membrane. We previously proposed (Kinnebrew et al., 2019) PTCH1 Smoothened by depleting accessible cholesterol from ciliary Using a new imaging-based assay to directly measure transport PTCH1, we find depletes outer leaflet plasma This terminated binding ligands or dissipation transmembrane potassium gradient. These...
Abstract The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine’s natural crinine‐type congeners, were evaluated in vitro against panel cancer cell lines various levels resistance pro‐apoptotic stimuli. Bulbispermine, haemanthamine, and haemanthidine showed the most potent antiproliferative activities as determined by MTT colorimetric assay. Among analogues, only C1,C2‐dicarbamate derivative exhibited...
Methods for the enantioselective conversion of D-xylose to differentially protected myo-inositol and L-chiro-inositol have been developed. The key transformation is a highly diastereoselective intramolecular SmI(2)-promoted pinacol coupling. stereoselectivity was extremely dependent on conditions, suggesting change in mechanism. Preliminary mechanistic experiments possible explanations this behavior are discussed.
Short stereoselective syntheses of various cyclitols, including the derivatives conduritol B, F, myo-inositol, and chiro-inositol have been accomplished. The key steps in are a ring-closing metathesis process diastereodivergent organometallic addition to d-xylose-derived aldehyde.
Abstract Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol not just but also sufficient to activate signaling by Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. influences Hh directly activating Smoothened (SMO), an orphan GPCR transmits signal across membrane all animals. Unlike most GPCRs, which are regulated through their heptahelical transmembrane domains, SMO activated its extracellular...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract Transmission of the Hedgehog signal across plasma membrane by Smoothened is proposed to be triggered its direct interaction with cholesterol. But how cholesterol, an abundant lipid, regulated tightly enough control a signaling system that can cause birth defects and cancer? Using toxin-based sensors distinguish between distinct pools we find here activation are driven biochemically defined fraction termed accessible Increasing cholesterol levels depletion sphingomyelin, which...