A5068563937- Cancer, Hypoxia, and Metabolism
- Cancer Mechanisms and Therapy
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Acute Myeloid Leukemia Research
- Advances in Cucurbitaceae Research
- Cancer-related Molecular Pathways
- Vitamin D Research Studies
- Pluripotent Stem Cells Research
- Barrier Structure and Function Studies
- Polysaccharides and Plant Cell Walls
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Retinoids in leukemia and cellular processes
- Chronic Myeloid Leukemia Treatments
- Cellular Mechanics and Interactions
- Radiopharmaceutical Chemistry and Applications
- CRISPR and Genetic Engineering
- Science, Research, and Medicine
- Cancer Cells and Metastasis
- S100 Proteins and Annexins
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
Board of the Swiss Federal Institutes of Technology
2024
ETH Zurich
2022-2024
University Hospital of Basel
2019-2023
University of Basel
2019-2023
Friedrich Miescher Institute
2022-2023
Tokushima Bunri University
2020
Cedars-Sinai Medical Center
2007-2015
University of California, Los Angeles
2008-2014
Shantou University Medical College
2013
Shantou University
2013
Somatic mutations in the spliceosome gene ZRSR2-located on X chromosome-are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved recognition of 3'-splice site during early stages assembly; however, its precise role RNA splicing has remained unclear. Here we characterize as an essential component minor (U12 dependent) assembly. shRNA-mediated knockdown leads to impaired U12-type introns and RNA-sequencing MDS bone marrow reveals that loss activity causes increased mis-splicing....
Self-organizing neural organoids grown from pluripotent stem cells
Abstract Pancreatic cancer is an aggressive malignancy that generally refractory to chemotherapy, thus posing experimental and clinical challenges. In this study, the antiproliferative effect of triterpenoid compound cucurbitacin B was tested in vitro vivo against human pancreatic cells. Dose-response studies showed drug inhibited 50% growth seven cell lines at 10−7 mol/L, whereas clonogenic significantly 5 × 10−8 mol/L. Cucurbitacin caused dose- time-dependent G2-M-phase arrest apoptosis...
The Ca2+-independent immunoglobulin-like molecule nectin first forms cell-cell adhesion and then assembles cadherin at nectin-based sites, resulting in the formation of adherens junctions (AJs). Afadin is a nectin- actin filament-binding protein that connects to cytoskeleton. Here, we studied roles modes action afadin AJs cultured MDCK cells. trans-interaction assembled E-cadherin, which associated with p120ctn, β-catenin, α-catenin, sites an afadin-independent manner. However, E-cadherin...
Par-3 is a cell-polarity protein that regulates the formation of tight junctions (TJs) in epithelial cells, where claudin major cell-cell adhesion molecule (CAM). TJs are formed at apical side adherens (AJs), E-cadherin and nectin CAMs. We have revealed first forms adhesions, then recruits cadherin to nectin-based sites form AJs subsequently TJs. The cytoplasmic tail binds afadin Par-3. Afadin cooperatively with nectin. Here, we studied role these by using Par-3-knockdown MDCK cells. was...
Patterning of the neural tube establishes midbrain and hindbrain structures that coordinate motor movement, process sensory input, integrate cognitive functions. Cellular impairment within these underlie diverse neurological disorders, in vitro organoid models promise inroads to understand development, model disease, assess therapeutics. Here, we use paired single-cell transcriptome accessible chromatin sequencing map cell composition regulatory mechanisms hindbrain. We find existing...
Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-γ-2 (LAMC2) epithelial basement membrane protein involved in cell migration and tumor invasion might represent ideal target for the development of novel therapeutic approaches ATC.The objective investigation was to study role LAMC2 ATC tumorigenesis.LAMC2 expression evaluated by RT-PCR, Western blotting, immunohistochemistry specimens, adjacent noncancerous tissues, lines. The short...
Abstract Brain organoids enable the mechanistic study of human brain development, and provide opportunities to explore self-organization in unconstrained developmental systems. Here, we establish long-term, live light sheet microscopy on unguided generated from fluorescently labeled induced pluripotent stem cells, which enables tracking tissue morphology, cell behaviors, subcellular features over weeks organoid development. We a novel dual-channel, multi-mosaic multi-protein labeling...
Cells assemble fibronectin, the major extracellular matrix (ECM) protein, into fibrillar matrices, which serve as 3D architectural scaffolds to provide, together with other ECM proteins tissue-specific environments. Although recent approaches enable bioengineer fibronectin matrices in vitro, it remains elusive how can be co-assembled complex that recapitulate compositions and cellular responses. Here, we introduce engineering of fibronectin-templated complemented proteins, including...
19-nor-14-epi-23-yne-1,25(OH)(2) D(3) (inecalcitol) is a unique vitamin analog. We evaluated the activity of inecalcitol in human prostate cancer model system. The analog was 11-fold more potent than 1,25(OH)(2) causing 50% clonal growth inhibition androgen-sensitive LNCaP cells. Inecalcitol, , reduced dose-dependent manner expression levels transcription factor ETS variant 1 and serine/threonine protein kinase Pim-1, both which are upregulated cancer. Remarkably, dose challenge experiments...
Morphogens, secreted signalling molecules that direct cell fate and tissue development, are used to neuroepithelial progenitors towards discrete regional identities across the central nervous system. Neural tissues derived from pluripotent stem cells in vitro (neural organoids) provide new models for studying neural regionalization, however, we lack a comprehensive survey of how developing human neuroepithelium responds morphogen cues. Here, produce detailed map morphogen-induced effects on...
Upon binding of platelet-derived growth factor (PDGF), PDGF receptor is autophosphorylated at tyrosine residues in its cytoplasmic region, which induces the activation diverse intracellular signaling pathways such those involving Ras-ERK, c-Src, and Rap1-Rac. Signaling through activated Ras-ERK promotes cell cycle proliferation. The sequential Rap1 Rac affects cellular morphology formation leading-edge structures, including lamellipodia, peripheral ruffles, focal complexes, resulting...
The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ C/EBPε double-knockout (bbee) mice compared their phenotypes to those single deficient (bbEE BBee) wild-type (BBEE) mice. bbee were highly susceptible fatal infections died within 2–3 months. Morphologically, neutrophils blocked at the myelocytes/metamyelocytes stage, clonogenic assays bone marrow cells...
Afadin is an actin-filament-binding protein that binds to nectin, immunoglobulin-like cell-cell adhesion molecule, and plays important role in the formation of adherens junctions. Here, we show afadin, which did not bind nectin was localized at leading edge moving cells, has another role: enhancement directional, but random, cell movement. When NIH3T3 cells were stimulated with platelet-derived growth factor (PDGF), afadin colocalized PDGF receptor, alphavbeta3 integrin nectin-like...
Aberrantly activated c-MET signaling occurs in several cancers, promoting the development of inhibitors. In this study, we found that eight thyroid cancer cell lines (including six anaplastic lines) have prominent expression protein. Fifty percent (four eight) were growth inhibited by two small molecule inhibitors (tivantinib and crizotinib) associated with apoptosis G(2)-M cell-cycle arrest. However, crizotinib did not inhibit 50% proliferation cells (SW1736 TL3) at a concentration which...
Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from primary ATC and its lymph node metastasis, investigated the molecular factors genomic changes associated with tumor growth.
A genome-wide PiggyBac transposon-mediated screen and a resistance in PIK3CAH1047R-mutated murine tumor model reveal NF1 loss mammary tumors resistant to the phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor alpelisib. Depletion of PIK3CAH1047R breast cancer cell lines patient-derived organoid shows that reduces sensitivity PI3Kα inhibition correlates with enhanced glycolysis lower levels reactive oxygen species (ROS). Unexpectedly, antioxidant N-acetylcysteine (NAC) sensitizes...