A5027886122- Hippo pathway signaling and YAP/TAZ
- Occupational and environmental lung diseases
- Wnt/β-catenin signaling in development and cancer
- Mast cells and histamine
- NF-κB Signaling Pathways
- Inflammatory mediators and NSAID effects
- Gene Regulatory Network Analysis
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Renal and related cancers
- Click Chemistry and Applications
- Single-cell and spatial transcriptomics
- Cellular Mechanics and Interactions
- Blood Coagulation and Thrombosis Mechanisms
- Venous Thromboembolism Diagnosis and Management
- Liver physiology and pathology
- Cellular transport and secretion
- Blood properties and coagulation
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Galectins and Cancer Biology
- Plant Surface Properties and Treatments
- Microbial metabolism and enzyme function
- melanin and skin pigmentation
VIB-KU Leuven Center for Cancer Biology
2013-2025
KU Leuven
2013-2022
Vlaams Instituut voor Biotechnologie
2018-2020
The University of Texas MD Anderson Cancer Center
2005-2013
The University of Texas at Austin
2001
The University of Texas Health Science Center at Houston
1998-2001
Academia Sinica
2000
Institute of Biomedical Sciences, Academia Sinica
1999
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
1993-1996
Defects in apical-basal cell polarity and abnormal expression of determinants are often associated with cancer vertebrates. In Drosophila , can cause neoplastic phenotypes, including loss overproliferation. However, the pathways through which affect growth poorly understood. Here, we investigated mechanism by apical determinant Crumbs (Crb) affects imaginal discs. Overexpression Crb causes severe overproliferation, found that similarly results overgrowth gain function caused defects Hippo...
The Hippo signaling pathway and its two downstream effectors, the YAP TAZ transcriptional coactivators, are drivers of tumor growth in experimental models. Studying mouse models, we show that can also exert a tumor-suppressive function. We found normal hepatocytes surrounding liver tumors displayed activation deletion Yap Taz these peritumoral accelerated growth. Conversely, hyperactivation triggered regression primary melanoma-derived metastases. Furthermore, whereas cells growing wild-type...
Abstract In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within liver lobule. However, it is unclear whether this spatial variation, called zonation, governed by a well-defined gene regulatory code. Here, using combination of single-cell multiomics, omics, massively parallel reporter assays deep learning, we mapped enhancer-gene networks across mouse cell types. We found that zonation affects expression chromatin accessibility in...
The pharmacological action of salicylate cannot be explained by its inhibition cyclooxygenase (COX) activity. In this report, the effects aspirin and sodium on COX-2 expressions in human umbilical vein endothelial cells foreskin fibroblasts were evaluated. Aspirin at therapeutic concentrations equipotently blocked mRNA protein levels induced interleukin-1β phorbol 12-myristate 13-acetate. suppressing effect was more pronounced cultured deprived fetal bovine serum for 24 h, suggesting that it...
Although it has been shown that mast cell-deficient mice have diminished innate immune responses against bacteria, the most important immunoprotective factors secreted from activated cells not identified. Mouse cell protease 6 is a tetramer-forming tryptase. This serine abundant in secretory granules and exocytosed upon bacterial challenge. Here we described generation of protease-6-null mouse. Our discovery lacking this neutral cannot efficiently clear Klebsiella pneumoniae their peritoneal...
The conserved Hippo tumor suppressor pathway is a key signaling that controls organ size in Drosophila. To date signal transduction cascade from the Cadherin Fat at plasma membrane into nucleus has been discovered. However, how regulated by extracellular signals poorly understood. not only regulates growth but also planar cell polarity, for which it interacts with Dachsous (Ds) Cadherin, and Four-jointed (Fj), transmembrane kinase modulates interaction between Ds Fat. Fj are expressed...
The Hippo signaling pathway is widely considered a master regulator of organ growth because the prominent overgrowth phenotypes caused by experimental manipulation its activity. Contrary to this model, we show here that removing transcriptional output did not impair ability mouse liver and Drosophila eyes grow their normal size. Moreover, activity effectors Yap/Taz/Yki correlate with cell proliferation, hyperactivation these induced gene expression programs recapitulate development....
Background and AimsThe Hippo pathway its downstream effectors YAP TAZ (YAP/TAZ) are heralded as important regulators of organ growth regeneration. However, different studies provided contradictory conclusions about their role during regeneration organs, ranging from promoting proliferation to inhibiting it. Here we resolve the function YAP/TAZ liver, where Hippo's in control has been studied most intensely.MethodsWe evaluated liver after carbon tetrachloride toxic injury mice with...
The Hippo tumor-suppressor pathway controls tissue growth in Drosophila and mammals by regulating cell proliferation apoptosis. includes the Fat cadherin, a transmembrane protein, which acts upstream of several other components that form kinase cascade culminates regulation gene expression through transcriptional coactivator Yorkie (Yki). Our previous work indicated Merlin (Mer) Expanded (Ex) are members act kinase. In contrast to this model, it was suggested Mer Ex primarily regulate...
Abstract The Hippo pathway and its downstream effectors, the YAP TAZ transcriptional coactivators, are deregulated in multiple different types of human cancer required for cell phenotypes vitro vivo, while largely dispensable tissue homeostasis adult mice. YAP/TAZ their main partner transcription factors, TEAD1–4 therefore promising anticancer targets. Because frequent hyperactivation caused by mutations components NF2 LATS2, mesothelioma is one prime predicted to be responsive YAP/TAZ-TEAD...
The anti-inflammatory actions of salicylates cannot be explained by inhibition cyclooxygenase (COX) activity. This study demonstrates that sodium salicylate at a therapeutic concentration suppressed COX-2 gene transcription induced phorbol 12-myristate 13-acetate and interleukin 1β inhibiting the binding CCAAT/enhancer-binding protein β to its promoter region COX-2. By contrast, did not inhibit nuclear factor κB-dependent induction tumor necrosis α. inhibitory effect was restricted...
Mast cell degranulation is a highly regulated, calcium-dependent process, which important for the acute release of inflammatory mediators during course many pathological conditions. We previously found that Synaptotagmin-2, calcium sensor in neuronal exocytosis, was expressed mast line. postulated this protein may be involved control cell-regulated and we generated Synaptotagmin-2 knock-out mice to test our hypothesis. cells from mutant animal conferred an abnormally decreased passive...
Organ development is directed by selector gene networks. Eye in the fruit fly Drosophila melanogaster driven highly conserved network referred to as "retinal determination network," composed of approximately 20 factors, whose core comprises twin eyeless (toy), (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, sufficient direct ectopic when misexpressed. While it well documented...
ABSTRACT The purpose of this investigation is to determine whether the levels cyclooxygenase‐2 (COX‐2) expression are cell cycle dependent. We used a serum‐starved human foreskin fibroblast model changes in COX‐2 mRNA, protein, and promoter activity response stimulation with interleukin‐1β (IL‐1β) phorbol 12‐myristate 13‐acetate (PMA) at G 0 , 1 S 2 /M phases cycle. IL‐1β (1 ng/ml) PMA (100 nM) induced robust cells, level declined progressively after cells had entered mRNA was 76%, 46%, 30%...
By using a mRNA differential display technique to search for salicylate suppressible genes, we identified cDNA in human foreskin fibroblasts, which by GenBankTM DNA data base shows sequence homology the recently reported cullin/Cdc53 (CUL) family especially CUL-3. We have cloned full-length CUL-3 (Hs-CUL-3) cDNA. It encodes 768-amino acid polypeptide and has predicted molecular weight of 88,939. The amino Hs-CUL-3 46% that its Caenorhabditis elegans ortholog, Ce-CUL-3, 27 23% Hs-CUL-1...
Significance The Hippo pathway is an important regulator of animal growth, and its effector, Yorkie (in flies) or YAP/TAZ mammals), drives the expression genes needed for cell proliferation survival. In effort to identify new regulators Yorkie, we performed a genetic modifier screen in Drosophila . this screen, identified RNA-binding protein Hrb27C as positive activity that modulates phosphorylation status. Additional experiments interacting proteins Glorund, Halfpint, Squid, Pabp2 negative...
Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing labeling methods lack compatibility with applications or suffer from low sensitivity, poor penetration, limited temporal resolution. Here, we fluorescently labeled dead cells Trypan Blue (TBlue) to detect single scattered generate whole-mount three-dimensional maps large areas necrotic during organ regeneration. TBlue effectively marked...
Cell type identity is encoded by gene regulatory networks (GRN), in which transcription factors (TFs) bind to enhancers regulate target expression. In the mammalian liver, lineage TFs have been characterized for main cell types, including hepatocytes. Hepatocytes cover a relatively broad cellular state space, as they differ significantly their metabolic state, and function, depending on position with respect central or portal vein liver lobule. It unclear whether this spatially defined...