A5025417194- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Click Chemistry and Applications
- Cholesterol and Lipid Metabolism
- Hedgehog Signaling Pathway Studies
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Synthetic Organic Chemistry Methods
- Gold and Silver Nanoparticles Synthesis and Applications
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Genetic and rare skin diseases.
- Neuroscience and Neuropharmacology Research
- Protein purification and stability
- Microtubule and mitosis dynamics
- Viral gastroenteritis research and epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Biotechnology and Related Fields
- Nanoparticle-Based Drug Delivery
- Peroxisome Proliferator-Activated Receptors
- Diet, Metabolism, and Disease
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Chromatin Dynamics
Broad Institute
2006-2009
Harvard University
2007-2009
Howard Hughes Medical Institute
2007-2009
Massachusetts Institute of Technology
2007-2009
Center for Systems Biology
2009
Massachusetts General Hospital
2009
Momenta Pharmaceuticals (United States)
2008
Boston University
2007
Brigham and Women's Hospital
2007
G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits assembly and interacts with via an ITFG motif, residue F17, the N protein. Prior studies examining impact G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, role this pathogenesis is unknown. Here, we use structural biochemical...
Stress granule formation is triggered by the release of mRNAs from polysomes and promoted action RNA-binding proteins G3BP1/2. granules have been implicated in several disease states, including cancer neurodegeneration. Consequently, compounds that limit stress or promote their dissolution potential as both experimental tools novel therapeutics. Herein, we describe two small molecules, G3BP inhibitor a b (G3Ia G3Ib), designed to bind specific pocket G3BP1/2 targeted viral inhibitors...
Nanoparticles bearing surface-conjugated targeting ligands are increasingly being explored for a variety of biomedical applications. The multivalent conjugation on the surface nanoparticles is presumed to enhance binding desired target. However, given complexities inherent in interactions nanoparticle surfaces with proteins, and structural diversity scaffolds ligands, our understanding how affects remains incomplete. Here, we use plasmon resonance (SPR) directly quantitatively study affinity...
Scavenger receptor, class B, type I (SR-BI), controls high-density lipoprotein (HDL) metabolism by mediating cellular selective uptake of lipids from HDL without the concomitant degradation particle. We previously identified in a high-throughput chemical screen intact cells five compounds (BLT-1−5) that inhibit SR-BI-dependent lipid transport HDL, but do not block binding to SR-BI on cell surface. Although these BLTs are widely used examine diverse functions SR-BI, their direct target(s),...
Phosphorylation of neurotransmitter receptors can modify their activity and regulate neuronal excitability. Cyclin-dependent kinase 5 (cdk5) is a proline-directed serine/threonine involved not only in development, but also synaptic function plasticity. Here we demonstrate that group I metabotropic glutamate (mGluRs), which modulate post-synaptic signaling by coupling to intracellular signal transduction pathways, are phosphorylated cdk5. In vitro assays reveal cdk5 phosphorylates mGluR5...
Abstract G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. prominent interactors of the nucleocapsid (N) protein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, functional consequences G3BP1-N interaction context infection remain unclear. Here we used structural and biochemical analyses define residues required for interaction, followed by structure-guided mutagenesis G3BP1 N selectively...
An epoxide derived from (−)-shikimic acid was attached to a solid support and used synthesize over 5000 diverse small molecules. Key transformations include Lewis acid-catalyzed opening with amines an intramolecular Heck reaction aryl iodides. Compounds this pathway were printed onto small-molecule microarrays screened for binding proteins. that bound Aurora A kinase characterized using surface plasmon resonance.
Treatment of atherosclerotic disease often focuses on reducing plasma LDL-cholesterol or increasing HDL-cholesterol. We examined in vitro the effects HDL receptor [scavenger class B type I (SR-BI)] activity three classes clinical and experimental HDL-cholesterol-elevating compounds: niacin, fibrates, HDL376. Fenofibrate (FF) HDL376 were potent (IC(50) approximately 1 microM), direct inhibitors SR-BI-mediated lipid transport cells liposomes reconstituted with purified SR-BI. FF, a prodrug,...
ABSTRACT Stress granule formation is triggered by the release of mRNAs from polysomes and promoted action paralogs G3BP1 G3BP2. G3BP1/2 proteins bind thereby promote condensation mRNPs into stress granules. granules have been implicated in several disease states, including cancer neurodegeneration. Consequently, compounds that limit or their dissolution potential as both experimental tools novel therapeutics. Herein, we describe two small molecules, referred to G3BP inhibitor a b (G3Ia...
Mycobacterium tuberculosis (Mtb) is the etiologic agent of and infects *32% human population.The cell envelope mycobacteria endowed with a number unique lipids that play an important role in its virulence.Large multifunctional proteins called polyketide synthases (PKSs) catalyze biosynthesis these lipids.PKSs are generally involved synthesis secondary metabolites various organisms their virulence factors unprecedented.PKSs require fatty acyl AMP ligases for activation utilization acid...