A5053043545- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Immune cells in cancer
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Single-cell and spatial transcriptomics
- Chronic Kidney Disease and Diabetes
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Dialysis and Renal Disease Management
- Endoplasmic Reticulum Stress and Disease
- Ion Transport and Channel Regulation
- Advanced Glycation End Products research
- Cardiac Fibrosis and Remodeling
- Cardiomyopathy and Myosin Studies
- Galectins and Cancer Biology
- Renin-Angiotensin System Studies
- Apelin-related biomedical research
- Aortic aneurysm repair treatments
National University of Singapore
2019-2024
Duke-NUS Medical School
2019-2024
National Neuroscience Institute
2024
Abstract The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4 + ) non-containing (XO4 − from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories ageing mice. microglial transcriptomes demonstrated dysregulated expression genes associated late onset AD. We further showed that the...
Key Points WWP2 expression is elevated in the tubulointerstitium of fibrotic kidneys and contributes to CKD pathogenesis progression. uncouples profibrotic activation cell proliferation renal myofibroblasts. controls mitochondrial respiration myofibroblasts through metabolic regulator peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Background Renal fibrosis a common pathologic end point that challenging reverse, are responsible for accumulation fibrillar collagen–rich...
Abstract Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in etiopathology but giving their heterogeneity and antagonizing roles macrophage subtypes targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator human murine show myeloid specific deletion...
Abstract Blood-based gene expression signatures could potentially be used as biomarkers for PD. However, it is unclear whether genetically-regulated transcriptomic can provide novel candidates use PD biomarkers. We leveraged on the Genotype-Tissue Expression (GTEx) database to impute whole-blood using summary statistics of three large-scale GWAS. A random forest classifier was with consensus imputed signature (IGS) discriminate between cases and controls. Outcome measures included Area under...
Abstract Background Transcriptomic changes in the essential tremor (ET)–associated cerebello‐thalamo‐cortical “tremor network” and their association to brain structure have not been investigated. Objective The aim was characterize molecular associated with network‐level imaging‐derived phenotypes (IDP) found ET. Methods We performed an imaging‐transcriptomic study British adults using imaging‐genome‐wide summary statistics (UK Biobank “BIG40” cohort; n = 33,224, aged 40–69 years). imputed...
Abstract Alzheimer’s disease (AD) is a heterogeneous that largely dependent on the complex cellular microenvironment in brain. This complexity impedes our understanding of how individual cell types contribute to progression and outcome. To characterize molecular functional diversity human AD brain we utilized single nuclei RNA- seq control patient brains order map landscape heterogeneity AD. We detail gene expression changes at level cells subclusters, highlighting specific contributions...
ABSTRACT The important role of microglia, the brain’s resident immune cells, in Alzheimer’s disease (AD) is now well recognized, however their molecular and functional diversity underlying mechanisms still remain controversial. To transcriptionally functionally characterize microglia AD aging, we isolated amyloid plaque-containing (XO4 + ) non-containing − from an mouse model. Transcriptomics analysis unveiled independent transcriptional trajectories ageing AD. XO4 microglial transcriptomes...
A major pathway in hypertension pathogenesis involves direct activation of ANG II type 1 (AT1) receptors the kidney, stimulating Na+ reabsorption. AT1 tubular epithelia control expression and stimulation transporters channels. Recently, we found reduced blood pressure enhanced natriuresis mice with cell-specific deletion smooth muscle (SMKO mice). Although impaired vasoconstriction preserved renal flow might contribute to exaggerated urinary excretion SMKO mice, considered whether...
Background: Tremor is related to abnormal structure of a cerebello-thalamo-cortical brain network. Previous essential tremor RNA-sequencing studies focused on the cerebellar cortex, despite broad acknowledgement that wider network involved in manifestation. We aimed characterise molecular changes associated with syndrome phenotypes. Methods: analysed imaging-transcriptomic associations among 184 MRI-derived phenotypes and imputed gene-expression profiles from 33,224 UK Biobank healthy...
Abstract Renal fibrosis is a common pathological endpoint in chronic kidney disease (CKD) that challenging to reverse. Although myofibroblasts are mainly responsible for the accumulation of fibrillar collagen-rich extracellular matrix (ECM) fibrotic kidney, recent studies have unveiled their diversity terms proliferative and characteristics. This could be linked with existence different metabolic states, myofibroblast reprogramming may contribute pathogenesis progression renal fibrosis....