A5039305084- MicroRNA in disease regulation
- RNA Research and Splicing
- Circular RNAs in diseases
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Muscle Physiology and Disorders
- Cancer-related molecular mechanisms research
- Cell death mechanisms and regulation
- Cardiomyopathy and Myosin Studies
- Aortic aneurysm repair treatments
- Plant Virus Research Studies
- Hearing, Cochlea, Tinnitus, Genetics
- Wnt/β-catenin signaling in development and cancer
- Cardiac Fibrosis and Remodeling
- Viral Infections and Immunology Research
- Endoplasmic Reticulum Stress and Disease
- Extracellular vesicles in disease
- Angiogenesis and VEGF in Cancer
- Cancer-related gene regulation
Seoul National University Hospital
2021-2024
Korea University
2015-2021
Boston Children's Hospital
2010-2020
Harvard University
2011-2020
Beijing University of Chinese Medicine
2014
Harvard Stem Cell Institute
2013-2014
Brigham and Women's Hospital
2013
Chongqing Medical University
2013
Shanghai Institutes for Biological Sciences
2012
Chinese Academy of Sciences
2012
MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators gene expression. Here, we investigated the function and molecular mechanisms miR-208 family miRNAs in adult mouse heart physiology. We found miR-208a, which is encoded within an intron alpha-cardiac muscle myosin heavy chain (Myh6), was actually member miRNA also included miR-208b, determined to be beta-cardiac (Myh7). These were differentially expressed heart, paralleling expression their...
Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death mature cardiomyocytes pathological cardiac conditions lack regeneration capacity primary causes heart failure mortality. However, how cardiomyocyte proliferation postnatal becomes suppressed remains largely unknown. The miR-17-92 cluster was initially identified as a human oncogene promotes proliferation. its role unknown.To...
The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response mechanical or pathological stress, the undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without number. However, molecular mechanism cardiac hypertrophy not fully understood.To identify and characterize microRNAs regulate remodeling.Screening for muscle-expressed are dynamically regulated during...
Rationale: In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, reduction cardiac dysfunction. The molecular pathways that regulate this are not fully understood. Objective: To explore the function microRNA-155 (miR-155) in hypertrophy remodeling. Methods Results: Our previous work identified miR-155 critical microRNA...
Abstract Skeletal muscle has remarkable regeneration capacity and regenerates in response to injury. Muscle largely relies on stem cells called satellite cells. Satellite normally remain quiescent, but injury or exercise they become activated proliferate, migrate, differentiate, fuse form multinucleate myofibers. Interestingly, the inflammatory process following activation of myogenic program are highly coordinated, with myeloid having a central role modulating cell regeneration. Here, we...
Abstract Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 the pivot (position 6). Here, by substituting nucleotide in with abasic spacers, which prevent pairing and alleviate steric hindrance, we eliminate while...
Abstract Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism clinical significance. Methods Herein, found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, investigated the roll vitro vivo. Results KAI1 was mainly rather than endothelial cells. It localized at membrane surface after palmitoylation by zDHHC4 enzyme...
Abstract POU4F3 , a member of the POU family transcription factors, commonly causes autosomal dominant deafness. Exome sequencing was used to identify four novel variants in (NM_002700.2), including c.564dupA: p.Ala189SerfsTer26, c.743T > C:p.Leu248Pro, c.879C A:p.Phe293Leu, and c.952G A:p.Val318Met, diverse aspects molecular consequences their protein expression, stability, subcellular localization, transcriptional activity were investigated. The expression three mutant proteins, encoded...
Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an
Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the undergoes cardiac remodeling. Pressure and volume overload in cause increased size (hypertrophic growth) of cardiomyocytes. Whereas regulatory pathways that activate hypertrophy have been well-established, molecular events inhibit repress are less known.To identify investigate novel regulators modulate hypertrophy.Here, we report identification, characterization, functional examination a...
Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show loss Xinβ, a newly-identified component ICDs, results cardiomyocyte proliferation defects cardiomyopathy. We uncovered role for Xinβ signaling via Hippo-YAP pathway by recruiting NF2 modulate cardiac function. In mutant...
ABSTRACT Background Abdominal aortic aneurysm (AAA) is a potentially lethal condition that often remains asymptomatic until it ruptures. Recent research suggests immune-inflammatory processes are associated with AAA development, yet the exact mechanisms remain unclear. Serum C-reactive protein (CRP) serves as prognostic marker for and various cardiovascular diseases. When CRP accumulates in damaged tissues, transforms into monomeric form, exacerbating tissue damage. Our previous study...
Abstract Hearing loss is one of the most prevalent sensory disorders, but no commercial biological treatments are currently available. Here, we identified an East Asia-specific founder mutation, homozygous c.220C>T mutation in MPZL2 , that contributes to a significant proportion hereditary deafness cases our cohort study. We found disease-causing could be targetable by adenine base editors (ABEs) enable A·T-to-G·C corrections without DNA double-strand breaks. To demonstrate this,...
Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is an ancient prokaryotic defense system that precisely cuts foreign genomic DNA under the control of a small number guide RNAs. The CRISPR-Cas9 facilitates efficient double-stranded cleavage has been recently adopted for genome editing to create or correct inherited genetic mutations causing disease. Congenital heart disease (CHD) generally caused by such as base substitutions, deletions,...
Small interfering RNAs (siRNAs) have been developed to intentionally repress a specific gene expression by directing RNA-induced silencing complex (RISC), mimicking the endogenous silencer, microRNAs (miRNAs). Although siRNA is designed be perfectly complementary an intended target mRNA, it also suppresses hundreds of off-targets way that miRNAs recognize targets. Until now, there no efficient avoid such off-target repression, although mode miRNA-like interaction has proposed. Rationally...
Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition viruses, play a role its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention children and adolescents. Its pathology is based on series of complex immune responses, including initial innate responses response entry, adaptive leading the development antigen-specific antibodies, autoimmune cellular injury caused by...
The ClC-K channels CLCNKA and CLCNKB are crucial for the transepithelial transport processes required sufficient urinary concentrations sensory mechanoelectrical transduction in cochlea. Loss-of-function alleles these associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome. Using a stepwise genetic approach encompassing whole-genome sequencing (WGS), we identified one...