A5046453739- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Prenatal Screening and Diagnostics
- Cancer-related Molecular Pathways
- 14-3-3 protein interactions
- Genomic variations and chromosomal abnormalities
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Fetal and Pediatric Neurological Disorders
- Chronic Lymphocytic Leukemia Research
- Microtubule and mitosis dynamics
- Heat shock proteins research
- Genetics and Neurodevelopmental Disorders
- Toxin Mechanisms and Immunotoxins
- Protein Degradation and Inhibitors
- interferon and immune responses
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- Biosensors and Analytical Detection
- Bioinformatics and Genomic Networks
Duke-NUS Medical School
2017-2025
National Cancer Centre Singapore
2017-2025
Singapore General Hospital
2025
South China Agricultural University
2024
Hunan Provincial Maternal and Child Health Hospital
2016-2021
National Health and Family Planning Commission
2020
Nanjing University of Aeronautics and Astronautics
2020
Peking University
2000-2018
Peking University People's Hospital
2018
Washington University in St. Louis
2012-2016
A new model of kinase regulation based on the assembly hydrophobic spines has been proposed. Changes in their positions can explain mechanism activation. Here, we examined mutations human cancer for clues about by focusing initially to Phe. We identified a selected number Phe small group kinases that included BRAF, ABL1, and epidermal growth factor receptor. Testing some these found one impaired ATP binding catalytic activity but promoted noncatalytic allosteric functions. Other functioned...
Because mutations in RAS and BRAF represent the most common found human tumors, identification of inhibitors has been a major goal. Surprisingly, new oncogenic specific inhibit cells transformed with mutated but paradoxically stimulate growth RAS. Here, we show that mechanism for activation is via drug-induced dimer formation between CRAF kinase suppressor Ras (KSR)1. To understand function KSR1, generated KSR1 mutant cannot bind ATP stabilizes closed, active conformation KSR1. Molecular...
Abstract Background Lysine succinylation is an emerging posttranslational modification that has garnered increased attention recently, but its role in gastric cancer (GC) remains underexplored. Methods Proteomic quantification of lysine was performed human GC tissues and adjacent normal by mass spectrometry. The mRNA protein levels lactate dehydrogenase A (LDHA) were analyzed qRT-PCR western blot, respectively. expression K222-succinylated LDHA measured tissue microarray the K222...
The Ser/Thr kinase RAF, particularly BRAF isoform is a dominant target of oncogenic mutations and many have been identified in various cancers. However, how these except V600E evade the regulatory machinery RAF protein hence trigger its oncogenicity remains unclear. Methods: In this study, we used mutagenesis, peptide affinity assay, immunoprecipitation, immunoblot, complementary split luciferase assay as well mouse xenograft tumour model to investigate function cooperatively regulated by...
Abstract Aberrant signaling due to mutations in the Epidermal Growth Factor Receptor (EGFR) kinase domain is implicated various diseases, including cancer. However, structural mechanisms underlying overactivation many rare EGFR remain poorly understood. Here, we benchmarked CHARMM and AMBER force fields compared simulations of asymmetric symmetric dimers establish a Molecular Dynamics (MD) protocol capable revealing mutant actional modes using relatively short simulations. This successfully...
Cancer-associated mutations in the kinase MEK1 increase its dimerization and stimulate RAF-independent signaling.
Although extensively studied for three decades, the molecular mechanisms that regulate RAF/MEK/ERK kinase cascade remain ambiguous. Recent studies identified dimerization of RAF as a key event in activation this cascade. Here, we show in-frame deletions β3-αC loop activate ARAF well BRAF and other oncogenic kinases by enforcing homodimerization. By characterizing these mutants, find has less allosteric catalytic activity than two isoforms, which arises from its non-canonical APE motif....
Lysophospholipids have emerged as biologically important chemoattractants capable of directing lymphocyte development, trafficking, and localization. Lysophosphatidic acid (LPA) is a major lysophospholipid found systemically, its levels are elevated in certain pathological settings, such cancer infections. In this study, we demonstrate that BCR signal transduction by mature murine B cells inhibited upon LPA engagement the LPA5 (GPR92) receptor via Gα12/13-Arhgef1 pathway. The inhibition...
Abstract TALL-1 is a member of the tumor necrosis factor family that binds to BCMA, TACI, and BAFF-R, three receptors mostly expressed by mature B lymphocytes. Previous studies have shown signaling critically involved in cell proliferation, maturation, progression lupus-like, autoimmune diseases. In this report, we performed cDNA subtractive hybridization experiments identify downstream genes up-regulated TALL-1. These indicated 10 genes, including interleukin (IL)-10, lymphocyte activation...
Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8 + T compared with dermal CD14 dendritic (DCs). Here we show that DCs instead prime a fraction of naïve into sharing the properties type 2 cytokine-secreting (TC2). Differential expression CD8-antagonist receptors on DCs, Ig-like transcript (ILT) inhibitory receptors, explains difference between two types DCs. Inhibition function LCs inhibited cytotoxic lymphocytes (CTLs) and enhanced TC2 generation. In addition,...
Proliferating cells display striking cell cycle dependence in sensitivity to gene activation by glucocorticoids; they are sensitive late gap 1/synthesis (G1/S) (late G1 and S phases) but resistant 2/mitotic (G2/M). Here we describe large cycle-dependent variations glucocorticoid receptor (GR) phosphorylation that accompany, may account for, the changes sensitivity. GRs basally phosphorylated undergo hyperphosphorylation after hormone-induced activation. Identified sites all N-terminal...
Abstract Exploring the mechanisms controlling lymphocyte trafficking is essential for understanding function of immune system and pathophysiology immunodeficiencies. The mammalian Ste20–like kinase 1 (Mst1) has been identified as a critical signaling mediator T cell migration, loss Mst1 results in immunodeficiency disease. Although known to support migration through induction polarization lamellipodial formation, downstream effectors are incompletely defined. Mice deficient actin-bundling...
Iron homeostasis is crucial for a variety of biological processes, but the role iron in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether involved maintaining pluripotency human PSCs (hPSCs). We found that intracellular depletion leads rapid downregulation NANOG and dramatic decrease self-renewal hPSCs as well spontaneous nonspecific differentiation. Moreover, long-term can result remarkable cell death via apoptosis necrosis pathways....
Abstract Hairy cell leukemia (HCL) is a B-lymphoma induced by BRAF(V600E) mutation. However, introducing in B-lymphocytes fails to induce hematological malignancy, suggesting that needs concurrent mutations drive HCL ontogeny. To resolve this issue, here we surveyed human genomic sequencing data. Together with previous reports, speculated the tumor suppressor TP53, P27, or PTEN restrict oncogenicity of B-lymphocytes, and therefore their loss-of-function facilitates BRAF(V600E)-driven Using...
Background: Skeletal dysplasias (SDs) are a heterogeneous group of genetic disorders that primarily affect bone and cartilage. This study aims to identify the causes for fetal SDs, evaluates diagnostic yield prenatal whole-exome sequencing (WES) this disorder. Methods: WES was performed on 38 fetuses with sonographically identified SDs normal results karyotype single nucleotide polymorphism (SNP) analysis. Candidate variants were selected by bioinformatics analysis, verified Sanger...