ShorterLab
@ShorterLab
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Countering deleterious phase transitions in ALS/FTD, PD, AD, and related disorders @Penn @PennMedicine @bb_upenn @BMBGGUPENN @PGGUPenn @PennNGG @CAMBUpenn
University of Pennsylvania
Joined January 2012
Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy: Cell Reports
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Directed evolution of an efficient and thermostable PET depolymerase:
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Ribosomes hibernate on mitochondria during cellular stress:
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Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs:
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Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired:
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Biomolecular condensates create phospholipid-enriched microenvironments:
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A highly structured RNA can rearrange the composition of a protein aggregate:
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Destabilization of the tips, unzipping and depolymerization of α-syn fibrils by Hsp110, Hsp70, and Hsp40:
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Liquid-liquid phase separation of light-inducible transcription factors increases transcription activation in mammalian cells and mice
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N-glycosylation as a eukaryotic protective mechanism against protein aggregation | Science Advances
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CryoET of β-amyloid and tau within postmortem Alzheimer’s disease brain:
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LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy:
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Genome organization around nuclear speckles drives mRNA splicing efficiency:
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Determinants that enable disordered protein assembly into discrete condensed phases:
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A rapid inducible RNA decay system reveals fast mRNA decay in P-bodies:
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Assembling membraneless organelles from de novo designed proteins:
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Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag:
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Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy:
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Daxx represents a new type of protein-folding enabler, excited that this work with Xiaolu Yang, @MarmorsteinLab, @JiabeiLin et al. is out in @Nature!
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Targeted protein relocalization via protein transport coupling:
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The molecular basis for cellular function of intrinsically disordered protein regions:
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Molecular insights into the interaction between a disordered protein and a folded RNA | PNAS
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High-yield vesicle-packaged recombinant protein production from E. coli
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Direct observation of prion-like propagation of protein misfolding templated by pathogenic mutants:
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mRNA location and translation rate determine protein targeting to dual destinations:
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Liquid-to-solid phase transition of oskar ribonucleoprotein granules is essential for their function in Drosophila embryonic development:
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Translation Initiation Site Profiling Reveals Widespread Synthesis of Non-AUG-Initiated Protein Isoforms in Yeast:
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Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro:
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Beyond aggregation: Pathological phase transitions in neurodegenerative disease
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Optogenetic dissection of transcriptional repression in a multicellular organism:
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MYC phase separation selectively modulates the transcriptome:
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Optogenetic control of mRNA localization and translation in live cells:
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Lifelong persistence of nuclear RNAs in the mouse brain | Science
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RNATACs: Multispecific small molecules targeting RNA by induced proximity:
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Friend or foe: The role of stress granule in neurodegenerative disease:
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Timing matters: A protective role of astrocyte reactivity in neurodegeneration:
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De novo engineering of intracellular condensates using artificial disordered proteins:
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Tuning Hsp104 specificity to selectively detoxify α-synuclein:
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Phase separation and ageing of glycine-rich protein from tick adhesive:
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Cryo-EM structures of amyloid-β and tau filaments in Down syndrome:
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Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits:
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α-Synuclein aggregation nucleates through liquid–liquid phase separation:
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Specific protein-RNA interactions are mostly preserved in biomolecular condensates | Science Advances
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TDP-43 condensation properties specify its RNA-binding and regulatory repertoire, excited that this collaborative work with @martinahallegg1 @ule_lab @Nicolas_Fawzi @JackRubien @YSPTSPS et al. is out in @CellCellPress:
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dsRNA formation leads to preferential nuclear export and gene expression:
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Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient: Cell
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Autophagy preferentially degrades non-fibrillar polyQ aggregates:
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Conformational ensembles of the human intrinsically disordered proteome:
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Always a constant source of inspiration @Penn, Virginia Lee, Alzheimer’s pioneer, wins $3 million Breakthrough Prize for work at @PennPathLabMed @PennAging!!
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Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease:
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Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice:
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Light-induced targeting enables proteomics on endogenous condensates:
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Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1:
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Microglia and complement mediate early corticostriatal synapse loss and cognitive dysfunction in Huntington’s disease:
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Mechanism of mammalian transcriptional repression by noncoding RNA:
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Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates:
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Direct observation of translational activation by a ribonucleoprotein granule:
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DEAD-box ATPases are global regulators of phase-separated organelles:
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Deciphering ER stress-unfolded protein response relationship by visualizing unfolded proteins in the ER:
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Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA:
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Alpha synuclein, the culprit in Parkinson disease, is required for normal immune function:
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RNA-driven phase transitions in biomolecular condensates: Molecular Cell
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Profiling stress-triggered RNA condensation with photocatalytic proximity labeling:
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Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models:
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De novo protein design—From new structures to programmable functions:
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Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components:
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A solid beta-sheet structure is formed at the surface of FUS droplets during aging:
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G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability: Molecular Cell
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How RNA-Binding Proteins Interact with RNA: Molecules and Mechanisms:
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Attenuating ribosome load improves protein output from mRNA by limiting translation-dependent mRNA decay:
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Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer’s Disease:
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Mouse oocytes sequester aggregated proteins in degradative super-organelles:
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A nascent peptide code for translational control of mRNA stability in human cells:
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Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics:
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The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions:
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RNA structure promotes liquid-to-solid phase transition of short RNAs in neuronal dysfunction:
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Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection:
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mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding:
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