A5016729762- RNA Research and Splicing
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- DNA Repair Mechanisms
- Heat shock proteins research
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Molecular Biology Techniques and Applications
- Nutrition and Health in Aging
- Ubiquitin and proteasome pathways
- Metastasis and carcinoma case studies
- Hereditary Neurological Disorders
- Cancer-related Molecular Pathways
- Supramolecular Self-Assembly in Materials
- Neurogenetic and Muscular Disorders Research
- Clinical Nutrition and Gastroenterology
- GDF15 and Related Biomarkers
- interferon and immune responses
- Genomics, phytochemicals, and oxidative stress
Westlake University
2023-2025
St. Jude Children's Research Hospital
2018-2021
Institute of Biophysics
2013-2018
Chinese Academy of Sciences
2013-2018
Czech Academy of Sciences, Institute of Biophysics
2018
Harvard Stem Cell Institute
2015
Brigham and Women's Hospital
2015
Harvard University
2015
University of Cincinnati
2015
Howard Hughes Medical Institute
2015
Stress granules (SGs) are non-membrane-bound RNA-protein that assemble through phase separation in response to cellular stress. Disturbances SG dynamics have been implicated as a primary driver of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), suggesting the hypothesis these diseases reflect an underlying disturbance material properties SGs. However, this concept has remained largely untestable available models assembly, which...
Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported GDF11/8 increase mouse serum.
Liquid-liquid phase separation (LLPS) is a mechanism of intracellular organization that underlies the assembly variety RNP granules. Fundamental biophysical principles governing LLPS during granule have been revealed by simple in vitro systems, but these systems limitations when studying biology complex, multicomponent Visualization granules cells has validated key this approach presents difficulties for interrogating features and provides limited ability to manipulate protein, nucleic acid,...
Prion-like proteins form multivalent assemblies and phase separate into membraneless organelles. Heterogeneous ribonucleoprotein D-like (hnRNPDL) is a RNA-processing prion-like protein with three alternative splicing (AS) isoforms, which lack none, one, or both of its two disordered domains. It has been suggested that AS might regulate the assembly properties by controlling incorporation regions in isoforms. This, turn, would modulate their activity downstream program. Here, we demonstrate...
Abstract Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role the antiviral process, owing to potent translational repressive effects ability trigger signal transduction; however, it is poorly understood how these differ from other stressors. Here we identify that TRIM25, known driver of ubiquitination-dependent innate immune response, critical marker SGs. TRIM25 undergoes liquid-liquid...
The mechanism by which protein aggregates are selectively degraded autophagy is poorly understood. Previous studies show that a family of Atg8-interacting proteins function as receptors linking specific cargoes to the autophagic machinery. Here we demonstrate during Caenorhabditis elegans embryogenesis, epg-7 functions scaffold mediating degradation several aggregates, including p62 homologue SQST-1, but has little effect on other autophagy-regulated processes. EPG-7 self-oligomerizes and...
Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as key enzyme that degrades ribosomal RNA in lysosomes. We found loss of rnst-2 causes accumulation rRNA proteins enlarged lysosomes both phenotypes are suppressed by blocking autophagy,...
Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche ternary complex based on the chimeric RET liquid–liquid phase separation. comprises rearranged kinase (RET fusion); adaptor (GRB2), and effector (SHC1). Together, they orchestrate cascade, which dependent tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its domain partner. promotes...
To date, stress granule studies mainly focus on cell models. The diversity of molecules in granules makes it challenging to uncover the function each molecule regulation. Here, we provide a protocol reconstitute with multi-components vitro. We describe steps for strain amplification, protein purification, and liquid-liquid phase separation (LLPS). multi-component reconstitution system constructed this also provides technique other condensate For complete details use execution protocol,...
Proteins with chemically regulatable phase separation are of great interest in the fields biomolecular condensates and synthetic biology. Intrinsically disordered proteins (IDPs) dominating building blocks which often lack orthogonality small-molecule regulation desired to create or membraneless organelles (MLOs). Here, we discover a well-folded globular protein, lipoate-protein ligase A (LplA) from E. coli involved lipoylation enzymes essential for one-carbon energy metabolisms, that...
Autophagy is an evolutionarily conserved catabolic process that involves the engulfment of cytoplasmic contents in a closed double-membrane structure, called autophagosome, and their subsequent delivery to vacuole/lysosomes for degradation. Genetic screens Saccharomyces cerevisiae have identified more than 30 autophagy-related (Atg) genes are essential autophagosome formation. Here we isolated novel autophagy gene, epg-9, whose loss function causes defective autophagic degradation variety...
Liquid-liquid phase separation (LLPS) has emerged as a crucial mechanism for cellular compartmentalization. One prominent example of this is the stress granule. Found in various types cells, granule biomolecular condensate formed through separation. It comprises numerous RNA and RNA-binding proteins. Over past decades, substantial knowledge been gained about composition dynamics granules. SGs can regulate signaling pathways have associated with human diseases, such neurodegenerative cancer,...
AbstractMacroautophagy (hereafter referred to as autophagy) involves the formation of a closed, double membrane structure, called autophagosome. Most Atg proteins that are essential for autophagosome evolutionarily conserved between yeast and higher eukaryotes. The functions some proteins, however, mediated by highly divergent in mammalian cells. In this study, we identified novel coiled-coil domain protein, EPG-8, plays an role autophagy pathway C. elegans. Mutations epg-8 cause defects...
Liquid-liquid phase separation (LLPS) mediated by G3BP1/2 proteins and non-translating mRNAs mediates stress granule (SG) assembly. We investigated the phylogenetic evolution of G3BP orthologs from unicellular yeast to mammals identified both conserved divergent features. The modular domain organization is generally conserved. However, invertebrate displayed reduced capacity for SG assembly in human cells compared vertebrate orthologs. demonstrated that protein-interaction network...