A5057041804- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- Cell Adhesion Molecules Research
- 3D Printing in Biomedical Research
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Genetics, Bioinformatics, and Biomedical Research
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Microfluidic and Bio-sensing Technologies
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Cell death mechanisms and regulation
- Wnt/β-catenin signaling in development and cancer
- Genomic variations and chromosomal abnormalities
- Pluripotent Stem Cells Research
- RNA modifications and cancer
Nanyang Technological University
2015-2025
National University of Singapore
1997-2020
Institute of Molecular and Cell Biology
1997-2002
MRC Laboratory of Molecular Biology
1993
University of Cambridge
1993
Joint profiling of transcriptome and chromatin accessibility within single cells allows for the deconstruction complex relationship between transcriptional states upstream regulatory programs determining different cell fates. Here, we developed an automated method with high sensitivity, assay single-cell regions (ASTAR-seq), simultaneous measurement whole-cell same cell. To show utility ASTAR-seq, profiled 384 mESCs under naive primed pluripotent as well a two-cell like state, 424 human...
PIX is a Rho-family guanine nucleotide exchange factor that binds PAK. We previously described two isoforms of differ in their N termini. Here, we report the identification new splice variant βPIX, designated β2PIX, dominant species brain and lacks region ∼120 residues with predicted coiled-coil structure at C terminus β1PIX. Instead, β2PIX contains serine-rich terminus. To determine whether these variants cellular function, studied effect expressing proteins HeLa cells. found plays key role...
Breast cancer (BC) cell lines are useful experimental models to understand biology. Yet, their relevance modelling remains unclear. To better the tumour-modelling efficacy of lines, we performed RNA-seq analyses on a combined dataset 2D and 3D cultures tumourigenic MCF7 non-tumourigenic MCF10A. our knowledge, this was first comprising MCF10A within same experiment, which facilitates elucidation differences between across culture types. We compared genes gene sets distinguishing from against...
Rho GTPases play major roles in the regulation of actin cytoskeleton, cell movement and cycle. PAK, one effector kinases these small GTPases, has long been associated with different types cancer. Therefore, it is likely that deregulation PAK activity or expression may contribute to development POPX2, a PP2C serine/threonine phosphatase, known dephosphorylate down regulate its activity. We find POPX2 expressed wide variety tumour lines, levels being highest more invasive MDA-MB-231 lowest...
The kinesin motors are important in the regulation of cellular functions such as protein trafficking, spindle organization and centrosome separation. In this study, we have identified POPX2, a serine-threonine phosphatase, an interacting partner KAP3 subunit kinesin-2 motor. motor is heterotrimeric complex composed KIF3A, KIF3B subunits KAP3, non-motor subunit, which binds cargo. Here report that phosphatase POPX2 negative regulator trafficking N-cadherin other cargoes; consequently, it...
Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem (iPSC) reprogramming. Here, we show that oocyte-enriched Tcl1 Tcl1b1 significantly enhance efficiency. Clonal analysis pluripotency biomarkers further oocyte improve Mechanistically, find enhancement effect depends on Akt, one its putative targets. In contrast, suppresses mitochondrial polynucleotide phosphorylase (PnPase) to promote Knockdown...
The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. changes are most obvious the adherent where stress fibres disassembled and cortical network becomes more prominent with concomitant increase cell rigidity as round up enter While regulatory connections between early mitotic events apparent, mechanisms that govern these links not well understood. Here, we report LIMK1 LIMK2, downstream effectors of RhoA/ROCK, regulate centrosome integrity astral...
Circular Dorsal Ruffles (CDRs) have been known for decades, but the mechanism that organizes these actin waves remains unclear. In this article we systematically analyze dynamics of CDRs on fibroblasts with respect to characteristics current models waves. We studied heterogeneously shaped cells and forced into disk-like morphology. show exhibit phenomena such as periodic cycles formation, spiral patterns, mutual wave annihilations are in accord an active medium description CDRs. On...
Abstract Endothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical models produce a spatial pattern of separated single cell, the salt-and-pepper pattern. However, classical cannot explain alternative tip-stalk patterning, such as that are two more We show involving only Delta and Notch proteins can also recapitulate experimental patterns...
Abstract Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents mouse (mESC) their differentiated counterparts, we find while zyxin lowly expressed mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression mESCs suppresses Oct4...
Apart from biochemical signals, tumour cells respond to biophysical and mechanical cues their environment. The forces the microenvironment could be in form of shear stress, tension, or solid stress compression. In this study, we explore effects compression on cells. Solid compression, a prevalent biomechanical stimulus accumulated during growth, has been shown enhance invasive metastatic phenotypes cancer However, underlying molecular mechanism that elicits aggressive phenotype, especially...
Oncogenic signaling drives unchecked proliferation by subverting cellular processes, often at the expense of genome integrity. To survive this inherent genotoxic stress, cancer cells have developed a critical reliance on non-oncogenic stress response pathways to safeguard their genome. Capitalizing therapeutic vulnerability, we exploited dependency stress-mitigating mechanisms during DNA replication identify naturally occurring compound - Molephantin. Here, derivatization Molephantin...
Chemoresistance is one of the leading causes that contributes to tumor relapse and poor patient outcome after several rounds drug therapy. The chemoresistance are multi-factorial. Ultimately, it balance pro- anti-apoptotic activities in cells. We have previously reported links between POPX2 serine/threonine phosphatase with cell motility invasiveness breast cancer Here, we show plays a role regulation apoptosis. effect on apoptosis centers inactivation TGF-β activated kinase (TAK1). TAK1...
Rho GTPases regulate cell morphogenesis and motility under the tight control of guanine nucleotide exchange factors (GEFs) GTPase-activating proteins (GAPs). However, underlying mechanism(s) that coordinate their spatiotemporal activities, whether separately or together, remain unclear. We show a prometastatic RhoGAP, ARHGAP8/BPGAP1, binds to inactive Rac1 localizes lamellipodia. BPGAP1 recruits RacGEF Vav1 epidermal growth factor (EGF) stimulation activates Rac1, leading polarized motility,...