A5000972332- RNA regulation and disease
- RNA Research and Splicing
- interferon and immune responses
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Advanced biosensing and bioanalysis techniques
- biodegradable polymer synthesis and properties
- Nanofabrication and Lithography Techniques
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- ATP Synthase and ATPases Research
- Circular RNAs in diseases
- Transplantation: Methods and Outcomes
- Chromosomal and Genetic Variations
- Advanced Biosensing Techniques and Applications
- Genomics and Chromatin Dynamics
- HER2/EGFR in Cancer Research
- Silk-based biomaterials and applications
- Amyotrophic Lateral Sclerosis Research
- Anodic Oxide Films and Nanostructures
- Atmospheric and Environmental Gas Dynamics
- Monoclonal and Polyclonal Antibodies Research
Korea Advanced Institute of Science and Technology
2018-2025
Boston Children's Hospital
2025
Broad Institute
2025
Harvard University
2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2025
Protein kinase R (PKR) is an immune response protein that becomes activated by double-stranded RNAs (dsRNAs). PKR overactivation associated with degenerative diseases inflammation, including osteoarthritis (OA), but the dsRNA activator remains largely unknown. Here, we find mitochondrial (mt-dsRNA) expression and its cytosolic efflux are facilitated in chondrocytes under OA-eliciting conditions, leading to innate activation. Moreover, mt-dsRNAs released extracellular space activate Toll-like...
Abstract Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 429 neurons from three C9ORF72 ALS, six FTD, seven AD, twenty-three neurotypical control brains revealed significantly increased burdens in somatic single nucleotide variant (sSNV) insertion/deletion (sIndel) all conditions. Mutational signature...
RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the gold standard identifying RBP repertoire of poly-adenylated RNAs, but such method ineffective capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA K1 antibody immunoprecipitation quantitative mass spectrometry to comprehensively identify bound cellular dsRNAs without external...
Changes in RNA splicing over the course of evolution have profoundly diversified functional landscape human genome. While DNA sequences proximal to intron-exon junctions are known be critical for splicing, impact distal intronic remains underexplored. Emerging evidence suggests that inverted pairs Alu elements can promote exon skipping by forming stem-loop structures. However, their prevalence and influence throughout remain unknown. Here, we present a systematic analysis across genome...
Secondary drug resistance stems from dynamic clonal evolution during the development of a prior primary resistance. This collateral type is often characteristic cancer recurrence. Yet, mechanisms that drive this and their drug-specific trajectories are still poorly understood. Using selection small-scale pharmacological screens, we find cells with acquired to microtubule-stabilizing paclitaxel develop tolerance epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), leading...
Reactive pentafluorophenyl acrylate (PFPA) polymer brushes grafted on silica particles were prepared using surface-initiated reversible addition and fragmentation chain transfer polymerization. The brush was successfully immobilized with antibody, then used for protein separation. immunoprecipitated proteins showed successful enrichment of target protein, reduced nonspecific background less contamination from eluted antibodies. To further improve recovery, the hydrophobic poly(PFPA) modified...
Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. Here, we show that an elevated fucosylation pan-cancer signature of both response resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed genes display widespread association with these In cell cultures, xenograft mouse models, patients, kinase inhibitors distinctively induced core secreted proteins less...
Reactive poly(pentafluorophenyl acrylate) (PPFPA)-grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA-grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody construct universal virus detection with enhanced sensitivity. PPFPA on silicon substrates is prepared, hydrophilicity modulated by partial substitution of the pentafluorophenyl units poly(ethylene glycol). Following dsRNA immobilization, prepared can distinguish long dsRNAs...
Abstract The outbreak of new viral strains promotes advances in universal diagnostic techniques for detecting infectious diseases with unknown sequence. Long double-stranded RNA (dsRNA), a hallmark infections, serves as virus marker prompt detection viruses genomes. Here, we report on-chip paper electrophoresis ultrafast screening diseases. Negatively charged RNAs pass through the micro and nanoscale pores cellulose order size under an external electric field applied to microfluidic channel....
Abstract Aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a non-enzymatic component required for the multi-tRNA synthetase complex. While exon skipping alternatively spliced variant of AIMP2 (AIMP2-DX2) compromises activity and associated with carcinogenesis, its clinical potential awaits further validation. Here, we found that AIMP2-DX2/AIMP2 expression ratio strongly correlated major cancer signaling pathways poor prognosis, particularly in acute myeloid leukemia...
Abstract Drug resistance remains the major culprit of therapy failure in disseminated cancers. Simultaneous to multiple, chemically different drugs feeds this resulting cancer relapse. Here, we investigate co-resistance signatures shared between antimitotic (AMDs) and inhibitors receptor tyrosine kinases (RTKs) probe mechanisms secondary resistance. We map ranks multiple drug pairs identified a more widespread occurrence EGFR-tyrosine kinase inhibitor (TKI) gefitinib hundreds cell lines...
ABSTRACT Protein kinase R (PKR) is an immune response protein that becomes activated by long double-stranded RNAs (dsRNAs). Several studies reported the misactivation of PKR in patients degenerative diseases including primary osteoarthritis (OA). However, molecular identity PKR-activating dsRNAs remains unknown. Here, we investigate role mitochondrial (mt-dsRNAs) development OA. We find to OA-mimicking stressors, cytosolic efflux mt-dsRNAs increased, leading activation and subsequent...
SUMMARY RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the golden standard identifying RBP repertoire, but such method ineffective capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA antibody immunoprecipitation quantitative mass spectrometry to comprehensively identify bound cellular dsRNAs without any external stimulus. Notably,...
Abstract Introns are found in all eukaryotes and one of the defining characteristics eukaryotes. After transcription, pre-mRNAs undergo splicing, introns excised lariat structure. Since degraded quickly after debranching, they have been considered as byproducts gene expression, their post-splicing role cells remains unclear. Here, we find that inhibition intron debranching process by depleting a enzyme, DBR1, results hyperactivation protein kinase R (PKR) due to accumulation lariat-derived...
We demonstrate a simple method to prepare poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads for antibody immobilization and subsequent immunoprecipitation (IP) application. The poly(PFPA) surface is prepared via two-step process. In the first step, 3-aminopropyltrimethoxysilane (APTMS) deposited as linker molecule onto surface. second homopolymer, synthesized reversible addition fragmentation chain transfer (RAFT) polymerization, through exchange reaction between...
Summary Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially introns and 3′ UTRs. Yet, biological significance of UTR IRAlus remains largely unknown. Here, we find that induce silencing genes involved essential signaling pathways. We utilize J2 antibody to directly capture map double-stranded RNA structure transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis IRAlus-mediated gene regulation. Notably, expression mouse double...