A5047100206- Barrier Structure and Function Studies
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Blood properties and coagulation
- Liver Disease and Transplantation
- 3D Printing in Biomedical Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic and Kidney Cyst Diseases
- Biochemical and Molecular Research
- Connexins and lens biology
- Advanced Glycation End Products research
- Anesthesia and Neurotoxicity Research
- Liver physiology and pathology
- Genetic Syndromes and Imprinting
- Coastal wetland ecosystem dynamics
- Cancer-related molecular mechanisms research
- Wound Healing and Treatments
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- Renal and related cancers
- Endoplasmic Reticulum Stress and Disease
- Mycobacterium research and diagnosis
- Genetics and Neurodevelopmental Disorders
- Pediatric Hepatobiliary Diseases and Treatments
National University of Singapore
2024
Agency for Science, Technology and Research
2008-2023
Institute of Molecular and Cell Biology
2001-2023
Wwtr1 is a widely expressed 14-3-3-binding protein that regulates the activity of several transcription factors involved in development and disease. To elucidate physiological role Wwtr1, we generated Wwtr1-/- mice by homologous recombination. Surprisingly, although known to regulate Cbfa1, factor important for bone development, show only minor skeletal defects. However, animals present with renal cysts lead end-stage Cysts predominantly originate from dilation Bowman's spaces atrophy...
ZO-1, ZO-2, and ZO-3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane such as claudins, junctional adhesion molecules, occludin to the actin cytoskeleton. Even though zonula occludens (ZO) among first TJ have been identified undergone extensive biochemical analysis, little is known about physiological roles of individual ZO in different tissues or during vertebrate development. Here, we show knockout mice lack an obvious phenotype. In contrast, embryos...
Tight junction integral membrane proteins such as claudins and occludin are tethered to the actin cytoskeleton by adaptor proteins, notably closely related zonula occludens (ZO) ZO-1, ZO-2, ZO-3. All three ZO have recently been inactivated in mice. Although ZO-3 knockout mice lack an obvious phenotype, animals deficient ZO-1 or ZO-2 show early embryonic lethality. Here, we rescue lethality of injecting ZO-2(-/-) stem (ES) cells into wild-type blastocysts generate viable chimera. ES...
The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated adaptor that essential for the structural regulatory functions of tight junctions in epithelial cells their absence leads to early embryonic lethality mouse models. Here, we use embryoid body, an vitro peri-implantation embryogenesis model, elucidate dissect roles play morphogenesis de novo junction assembly. Through generation individual or combined null bodies, show dual deletion prevents formation, resulting...
ZO-1/Tjp1 is a cytosolic adaptor that links tight junction (TJ) transmembrane proteins to the actin cytoskeleton and has also been implicated in regulating cell proliferation differentiation by interacting with transcriptional regulators signaling proteins. To explore possible roles for ZO-1 mouse embryonic stem cells (mESCs), we inactivated locus homologous recombination. The lack of was found affect mESC self-renewal presence leukemia-inhibiting factor (LIF) Bmp4 or following removal...
Abstract TJP2/ZO-2 -inactivating mutations in humans cause progressive cholestatic liver disease. Liver-specific deletion of Tjp2 the mouse ( cKO mice) leads to mild cholestasis without an overt degradation bile-blood barrier (BBB). These mice are more susceptible cholic acid (CA) induced injury. Interestingly, while initially also susceptible, develop tolerance a DDC-supplemented diet. The DDC diet induces exacerbated ductular reaction mice, which arises from transdifferentiation...
Abstract ZHX3, which encodes for a transcriptional repressor, is associated with fasting blood glucose (FBG) levels and increased type 2 diabetes (T2D) risk but its role in cell types involved metabolism not well understood. Here, we show that the deletion of ZHX3 human pancreatic β-cell line EndoC-βH1 did impair glucose-stimulated insulin secretion (GSIS) nor perturb transcriptome. On other hand, found represses expression gluconeogenic genes PCK1 G6PC1 hepatoma HepG2. Transcriptomic...
BACKGROUND & AIMS Tight junctions (TJs) establish tissue barriers that maintain osmotic homeostasis and, in the liver, isolate bile flow from blood circulation. ZO-2/Tjp2 is a scaffold protein tethers TJ transmembrane proteins to actin cytoskeleton. Missense mutations Tjp2 have recently been shown cause progressive cholestatic liver disease humans. However, underlying mechanisms still remain elusive. To study role of disease, we generated and characterized mice lacking hepatocytes,...