A5054437186- Pancreatic function and diabetes
- Renal and related cancers
- Erythrocyte Function and Pathophysiology
- Biomedical Research and Pathophysiology
- Liver physiology and pathology
- Pancreatic and Hepatic Oncology Research
- Pluripotent Stem Cells Research
- Pediatric Hepatobiliary Diseases and Treatments
- Congenital heart defects research
- Neonatal Health and Biochemistry
- Extracellular vesicles in disease
- Blood properties and coagulation
- TGF-β signaling in diseases
- Amino Acid Enzymes and Metabolism
- Genetic and Kidney Cyst Diseases
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Estrogen and related hormone effects
- Single-cell and spatial transcriptomics
- Pancreatitis Pathology and Treatment
- S100 Proteins and Annexins
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Circular RNAs in diseases
- Thyroid Cancer Diagnosis and Treatment
de Duve Institute
2015-2025
UCLouvain
2011-2023
Johns Hopkins Medicine
2005
Johns Hopkins University
2005
Fund for Scientific Research
2004
The Honourable Society of Lincoln's Inn
1999-2001
Research Institute of Molecular Pathology
2000
Cancer Research Institute
2000
Vanderbilt University
1999
During liver development, hepatocytes and biliary cells differentiate from common progenitors called hepatoblasts. The factors that control hepatoblast fate decision are unknown. Here we report a gradient of activin/TGFbeta signaling controls differentiation. High is required near the portal vein for differentiation cells. Onecut transcription HNF-6 OC-2 inhibit in parenchyma, this allows normal hepatocyte In absence factors, shape perturbed hepatoblasts into hybrid display characteristics...
c-Raf-1 is a major effector of Ras proteins, responsible for activation the ERK MAP kinase pathway and critical regulator both normal growth oncogenic transformation. Using an inducible form Raf in MDCK cells, we have shown that sustained alone able to induce transition from epithelial mesenchymal phenotype. promoted invasive collagen gels, characteristic malignant cells; this was dependent on operation autocrine loop involving TGFbeta, whose secretion induced by Raf. TGFbeta inhibition...
Smad4 plays a pivotal role in all transforming growth factor beta (TGF-beta) signaling pathways. Here we describe six widely expressed alternatively spliced variants of human with deletions different exons the linker, region that separates two well-conserved MH1 and MH2 domains. All these form complexes activated Smad2 Smad3 are incorporated into DNA-binding transcription Fast-1, regardless amount linker they contain. However, sequences encoded by 5 to 7 essential for transcriptional...
In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in conducting airways. Epithelial-to-mesenchymal transition (EMT) has been recently suggested COPD, but the mechanisms relationship to peribronchial remain unclear. We hypothesised that de-differentiation of COPD respiratory epithelium through EMT could participate airway thereby, obstruction. Surgical lung tissue primary broncho-epithelial cultures (in air-liquid interface...
Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable self-assembly, building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report functional vascularized mouse gland construct from embryonic spheroids proof concept. Based on self-assembly principle, generated starting (TS) allantoic (AS) source thyrocytes endothelial...
During pancreatic organogenesis endocrine cells arise from non self-renewing progenitors that express Ngn3. The precursors give rise to Ngn3+ are presumably located within duct-like structures. However, the nature of such is poorly understood. We show that, at E13-E18, embryonic stage during which major burst beta-cell neogenesis takes place, duct Hnf1beta, product maturity-onset diabetes young type 5 (MODY5) gene. this invariably cluster with mitotically competent Hnf1beta+ cells, and often...
Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation expression of cyclin D1 proliferating nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny proximal tubular cells (OK cells), ZONAB PCNA levels decreased in parallel inversely correlated with...
Ductal plate malformations (DPMs) are developmental anomalies considered to result from lack of ductal remodeling during bile duct morphogenesis. In mice, development is initiated by the formation primitive structures lined two cell types, namely cells and hepatoblasts. During remodeling, mature ducts as a differentiation hepatoblasts cholangiocytes. Here, we report this process conserved in human fetal liver. These findings prompted us evaluate how DPMs develop three mouse models, mice with...
Cystinosis, a main cause of Fanconi syndrome, is reproduced in congenic C57BL/6 cystinosin knockout (KO) mice. To identify the sequence pathogenic and adaptation mechanisms nephropathic cystinosis, we defined onset syndrome KO mice between 3 6 months age analyzed correlation with structural functional changes proximal tubular cells (PTCs), focus on endocytosis ultrafiltrated disulfide-rich proteins as key source cystine. Despite considerable variation at same age, typical event sequences...
MarvelD3 is a transmembrane component of tight junctions, but there little evidence for direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, components link junction to such pathways are not well understood. In this paper, we show dynamic regulator MEKK1–c-Jun NH2-terminal kinase (JNK) pathway. Loss expression differentiating Caco-2 cells resulted increased migration and proliferation, whereas...
Abstract In vitro models of the pancreas can aid in developing therapies for pancreatic diseases. Nonetheless, most tissue engineering is limited to insulin‐secreting β‐cells or adenocarcinoma models. Combining all essential components, including exocrine, endocrine, and blood vasculature, crucial recapitulate native organization. this study, extrusion‐based 3D bioprinting create constructs containing both endocrine exocrine compartments exploited. Mouse pluripotent stem cell‐derived...
Generation of pancreatic precursor cells in the endoderm is controlled by a network transcription factors. Hepatocyte nuclear factor-6 (HNF6) key player this network, because it controls initiation expression and duodenal homeobox 1 (Pdx1), earliest marker cells. To further characterize we have investigated how HNF6 mouse endoderm, using vitro vivo protein-DNA interaction techniques combined with electroporation, transgenesis, gene inactivation embryos. We delineated Hnf6 regulatory regions...
YBX3/ZONAB/CSDA is an epithelial-specific transcription factor acting in the density-based switch between proliferation and differentiation. Our laboratory reported overexpression of YBX3 clear cell renal arcinoma (ccRCC), as part a wide study regulation vitro vivo. The preliminary data was limited to 5 cases, which only 3 could be compared paired normal tissue, beta-Actin used sole reference normalize gene expression. We thus decided re-evaluate expression by real-time-PCR larger panel...
The extracellular vesicle release in red blood cell concentrates reflects progressive accumulation of storage lesions and could represent a new measure to be implemented routinely centres addition haemolysis. Nevertheless, there is currently no standardized isolation protocol. In previous publication, we developed reproducible ultracentrifugation-based protocol (20,000 × g protocol) that allows classify into three cohorts according their vesiculation level. Since this was not adapted meet...
At early stages of tumorigenesis, the transforming growth factor-β (TGF-β) signaling pathway is thought to have tumor suppressor activity as a result its ability arrest epithelial cells. Smad4 plays pivotal role in TGF-β and has been identified suppressor, being mutated or deleted ∼50% pancreatic carcinomas 15% colorectal cancers. A nonsense mutation generating C-terminal truncation 38 amino acids protein adenocarcinoma (Hahn, S. A., Schutte, M., Hoque, A. T., Moskaluk, C. da Costa, L....
Abstract Background The exocrine pancreas is composed of a branched network ducts connected to acini. They are lined by monolayered epithelium that derives from the endoderm and surrounded mesoderm-derived mesenchyme. morphogenic mechanisms which ductal established as well signaling pathways involved in this process poorly understood. Results By morphological analyzis wild-type mutant mouse embryos using cultured embryonic explants we investigated how epithelial morphogenesis takes place...
Unlimited replicative potential is one of the hallmarks cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) frequently overexpressed because activating mutations in its promoter, suggesting that telomerase necessary for melanoma development. We observed, however, a subset metastases and derived cell lines had no telomere maintenance mechanism. Early passages latter displayed long telomeres progressively shortened fused before death. propose that, during formation, oncogenic...
Abstract Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which impaired infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism the most frequent earliest endocrine complication of cystinosis unknown. We here defined early alterations Ctns−/− mice thyroid identified subcellular molecular mechanisms. At 9 months, T4...