A5028573028- Autophagy in Disease and Therapy
- Cervical Cancer and HPV Research
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- Sirtuins and Resveratrol in Medicine
- Nuclear Structure and Function
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Cardiovascular Function and Risk Factors
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Cancer Cells and Metastasis
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Genetics, Aging, and Longevity in Model Organisms
- FOXO transcription factor regulation
- Smoking Behavior and Cessation
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Dietary Effects on Health
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Genomics and Chromatin Dynamics
National University of Singapore
2001-2024
Institute of Molecular and Cell Biology
2000-2022
Agency for Science, Technology and Research
2017-2022
National University Health System
2019-2021
Institute of Medical Biology
2015-2021
Nanyang Technological University
2012-2020
Renal Association
2019
University of California, San Diego
2016-2017
VA San Diego Healthcare System
2016
Massachusetts General Hospital
1999-2014
Aggregation and cleavage are two hallmarks of Tau pathology in Alzheimer disease (AD), abnormal fragmentation is thought to contribute the nucleation paired helical filaments. Clearance abnormally modified protein could occur by ubiquitin–proteasome autophagy–lysosomal pathways, major routes for degradation cells. There a debate on which these pathways contributes clearance aggregates formed AD. Here, we demonstrate an inducible neuronal cell model tauopathy that system both into...
Although ubiquitin-enriched protein inclusions represent an almost invariant feature of neurodegenerative diseases, the mechanism underlying their biogenesis remains unclear. In particular, whether topology ubiquitin linkages influences dynamics is not well explored. Here, we report that lysine 48 (K48)- and 63 (K63)-linked polyubiquitination, as monoubiquitin modification contribute to inclusions. K63-linked polyubiquitin most consistent enhancer formation. Under basal conditions, ectopic...
Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism. The underlying mechanism of pathogenesis parkin-associated Parkinson's disease (PD) is thought to be due the loss parkin's E3 ubiquitin ligase activity. A subset missense and nonsense point mutations that span entire gene represent numerous inheritance patterns parkin-linked PD were investigated for their activity, localization ability bind, ubiquitinate effect degradation two substrates, synphilin-1...
Abstract The CCAAT/enhancer binding protein α (C/EBPα) is vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA loss-of-function mutations identified in acute myeloid leukemia patients support a tumor suppressor role C/EBPα. Recent work showed reductions of C/EBPα levels human carcinoma with the correlating to size progression. We investigated potential reactivating c/ebpα expression during carcinogenesis prevent cell have developed knock-in...
Chaperone-mediated autophagy (CMA) is an intracellular catabolic pathway that mediates the degradation of a selective subset cytosolic proteins in lysosomes ([Dice, 2007][1]; [Cuervo, 2010][2]; [Kon and Cuervo, 2010][3]; [Orenstein 2010][4]). The term (or self-eating)
Aggresomes are juxtanuclear inclusion bodies that have been proposed to act as staging grounds for the disposal of protein aggregates via autophagic route. To examine whether composition an aggresome influences its clearance by autophagy, we ectopically expressed a variety aggregation-prone proteins in cultured cells generate aggresomes differ their content. We found whereas generated expressing mutant huntingtin or tau, co-expressing synphilin-1 and α-synuclein, amenable those produced...
Hutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by mutation in LMNA, resulting truncated form of lamin A called progerin. Progerin triggers loss the heterochromatic marker H3K27me3, and senescence, which prevented telomerase. However, mechanism how progerin causes disease remains unclear. Here, we describe an inducible cellular system to model HGPS find that LAP2α (lamina-associated polypeptide-α) interacts with A, while its interaction significantly reduced....
Wnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential of glandular epithelia intestine and stomach, but their existence developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models identify uterus evaluate stem cell identity function. Lgr5 broadly expressed epithelium during embryogenesis,...
Lgr5+ crypt base columnar cells, the operational intestinal stem cells (ISCs), are thought to be dispensable for small (SI) homeostasis. Using a Lgr5-2A-DTR (diphtheria toxin receptor) model, which ablates with near-complete efficiency and retains endogenous levels of Lgr5 expression, we show that persistent depletion ISCs in fact compromises SI epithelial integrity reduces turnover vivo. In vitro, organoids unable establish or survive when continuously eliminated by adding DT media....
Loss of parkin function is a predominant cause familial Parkinsonism. Emerging evidence also suggests that expression variability may confer risk for sporadic Parkinson disease. We have recently demonstrated wide variety disease-linked stressors, including dopamine (DA), induce solubility alterations and promote its aggregation within the cell, phenomenon underlie progressive susceptibility brain to degeneration. The vulnerability stress-induced modification likely due abundance cysteine...