A5062422399- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Renal and related cancers
- RNA Research and Splicing
- Wound Healing and Treatments
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Hair Growth and Disorders
- Skin and Cellular Biology Research
- Cancer-related gene regulation
- Mitochondrial Function and Pathology
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Silk-based biomaterials and applications
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Probiotics and Fermented Foods
- Genomics and Rare Diseases
- Immune cells in cancer
- Nuclear Receptors and Signaling
- Plant Molecular Biology Research
- Mesenchymal stem cell research
National University of Singapore
2000-2024
Agency for Science, Technology and Research
2013-2024
National Skin Centre
2020-2023
Institute of Medical Biology
2009-2018
University of California, San Diego
2004-2010
Genome Institute of Singapore
2008
Albert Einstein College of Medicine
2007
Innsbruck Medical University
2007
Rutgers, The State University of New Jersey
2007
Massachusetts Institute of Technology
2004
Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE the leading cause fetal maternal morbidity mortality, its molecular etiology still unclear. Here, we show that ELABELA (ELA), an endogenous ligand apelin receptor (APLNR, or APJ), circulating hormone secreted by placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria elevated blood pressure due to defective placental angiogenesis....
The organization of chromatin affects all aspects nuclear DNA metabolism in eukaryotes. H3.3 is an evolutionarily conserved histone variant and a key substrate for replication-independent assembly. Elimination remodeling factor CHD1 Drosophila embryos abolishes incorporation into the male pronucleus, renders paternal genome unable to participate zygotic mitoses, leads development haploid embryos. Furthermore, CHD1, but not ISWI, interacts with HIRA cytoplasmic extracts. Our findings...
ABSTRACT To describe the phenomena of bacterial adhesion to intestinal cells and competition for between bacteria, mathematical equations based on a simple dissociation process involving finite number receptors cell surface were developed. The allow estimation maximum Lactobacillus sp. Escherichia coli that can adhere Caco-2 mucus; they also characterize affinity bacteria fecal mucus theoretical ratio two present in mixed suspension. rhamnosus GG E. TG1 appeared follow proposed kinetics,...
The core promoter is the ultimate target of vast network regulatory factors that contribute to initiation transcription by RNA polymerase II. Here we describe MTE (motif ten element), a new element appears be conserved from Drosophila humans. promotes II when it located precisely at positions +18 +27 relative A(+1) in initiator (Inr) element. sequences +22 are important for basal transcription, and region sufficient confer activity heterologous promoters. requires Inr, but functions...
Abstract The Wnt signaling pathway is necessary both for maintaining undifferentiated stem cells and directing their differentiation. In mouse embryonic (ESCs), preferentially maintains “stemness” under certain permissive conditions. T-cell factor 3 (Tcf3) a component of the dominant downstream effector in ESCs. Despite wealth knowledge regarding importance underlying functions, precise mechanistic explanation by which effects are mediated unknown. this study, we identified new regulatory...
Human embryonic stem cells (hESCs) regularly acquire nonrandom genomic aberrations during culture, raising concerns about their safe therapeutic application.The International Stem Cell Initiative identified a copy number variant (CNV) amplification of chromosome 20q11.21 in 25% hESC lines displaying normal karyotype.By comparing four cell paired for the presence or absence this CNV, we show that those containing amplicon have higher population doubling rates, attributable to enhanced...
There are considerable challenges in directly targeting the mutant p53 protein, given large heterogeneity of mutations clinic. An alternative approach is to exploit altered fitness cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs growth and patient-derived ovarian xenografts. Metabolome profiling reveals that induces mitochondrial uncoupling, which renders susceptible...
The RNA polymerase II core promoter is a diverse and complex regulatory element. To gain better understanding of the promoter, we examined motif 10 element (MTE), which located downstream transcription start site acts in conjunction with initiator (Inr). We found that MTE promotes binding purified TFIID to TAF6 TAF9 subunits appear be close proximity MTE. identify specific nucleotides contribute activity, performed detailed mutational analysis determined functional consensus sequence. These...
Abstract An effective wound management strategy needs accurate assessment of status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these such as immunohistochemistry quantitative polymerase chain reaction are usually laborious, resource‐intensive, disruptive. article reports development utilization mRNA nanosensors (i.e., NanoFlare) that topically applied on cutaneous...
In this work, we report the first hybrid nanosized photoinitiators with low cytotoxicity and migration by coupling of polyhedral oligomeric silsesquioxanes (POSS) to benzophenone derivatives. This new series were fully characterized showed many favorable properties such as uniform sizes, extremely tendency migrate, less effect on resin viscosity, enhanced thermal stability mechanical strength, increased photoactivity, significantly lower cell toxicity compared their corresponding molecules....
Ageing-related delays and dysregulated inflammation in wound healing are well-documented both human animal models. However, cellular molecular changes underlying this impairment progression not fully understood. In study, we characterised ageing-associated to macrophages wounds of young aged mice investigated transcriptomic differences that may impact the healing. Full-thickness created on dorsum C57BL/6J were excised Days 3 7 post-wounding for analysis by immunohistochemistry, flow...
The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected unclear. Our objective is to understand target selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in EGFP driven transcriptional activity at a response element from either p21 Puma promoter, induces...
During vertebrate gastrulation, a complex set of mass cellular rearrangements shapes the embryonic body plan and appropriately positions organ primordia. In zebrafish Xenopus, convergence extension (CE) movements simultaneously narrow axis mediolaterally elongate it from head to tail. This process is governed by polarized cell behaviors that are coordinated components non-canonical, β-catenin-independent Wnt signaling pathway, including Wnt5b transmembrane planar polarity (PCP) protein...
Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that polyamine regulator AMD1 is critical for embryonic cell self-renewal. The polyamines putrescine, spermidine, spermine essential organic cations play a role in wide array of cellular processes. Here, we explore promotion self-renewal identify new acts downstream polyamines: MINDY1. MINDY1 protein levels high (ESCs) dependent on levels. Overexpression...
Abstract The modulation of chromatin dynamics by ATP-dependent remodeling factors has been recognized as an important mechanism to regulate the balancing self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied effects a partial deletion gene encoding factor Chd1 that generates N-terminally truncated version mouse ESCs vitro well vivo . We found previously uncharacterized serine-rich region (SRR) at N-terminus is not required for assembly activity but it subject...
Abstract The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics generate membrane protrusions in response cell signaling. Adult mice lack IRSp53 fail regulate synaptic plasticity exhibit hippocampus-associated learning deficiencies. Here, we show 60% null embryos die at mid late gestation, indicating a vital function embryonic development. We find KO displayed pleiotropic phenotypes such as...
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The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation their progeny. This is accompanied changes in gene expression morphology that are orchestrated, part, epigenetic modifiers. Here, we define the role histone acetyltransferase KAT2A epidermal homeostasis provide comparative analysis reveals key functional divergence with its paralog KAT2B. In contrast to reported function KAT2B differentiation, supports undifferentiated state...
The hair follicle is a specialized appendage of the skin that critical for multiple functions, including thermoregulation, immune surveillance, and sebum production. Mammals are born with fixed number follicles develop embryonically. Postnatally, these undergo regenerative cycles regression growth recapitulate many embryonic signaling pathways. Furthermore, have direct impact on regeneration in homeostasis, cutaneous wound healing, disease conditions such as alopecia. Here, we review current...
Cellular differentiation during embryogenesis involves complex gene regulation to enable the activation and repression of genes. Here, we show that mesodermal competence is inhibited in Xenopus embryos depleted histones H3 H3.3, which fail respond Nodal/Activin signaling exhibit concomitant loss expression. We find transcriptional gastrula does not correlate with promoter deposition H3.3. Instead, gastrulation defects H3.3/H3-deficient are partially rescued concurrent depletion linker...
Post-translational modifications on nucleosomal histones represent a key epigenetic regulatory mechanism to mediate the complex gene expression, DNA replication, and cell cycle changes that occur in embryonic cells undergoing lineage specification, maturation, differentiation during development. Here, we investigated dynamics of 13 histone marks epidermal at three distinct stages skin development identified significant corresponded with maturation proliferative basal terminally...