A5041892653- Pancreatic function and diabetes
- Diabetes and associated disorders
- Endoplasmic Reticulum Stress and Disease
- Protein Tyrosine Phosphatases
- Diet, Metabolism, and Disease
- Immune Cell Function and Interaction
- Diabetes Management and Research
- Cell death mechanisms and regulation
- Metabolism, Diabetes, and Cancer
- Alzheimer's disease research and treatments
- Phagocytosis and Immune Regulation
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Gut microbiota and health
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Dendrimers and Hyperbranched Polymers
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Nuclear Receptors and Signaling
- MicroRNA in disease regulation
- Adipose Tissue and Metabolism
- Cytokine Signaling Pathways and Interactions
Université Libre de Bruxelles
2012-2025
Walloon Excellence in Lifesciences and Biotechnology
2023-2025
Instituto Murciano de Investigación Biosanitaria
2023
The University of Melbourne
2014-2021
Monash University
2012-2018
Australian Regenerative Medicine Institute
2018
St Vincent's Hospital
2014-2017
St Vincents Institute of Medical Research
2014-2017
St. Vincent's Hospital
2017
Saint Vincent's Catholic Medical Center
2017
Obesity is a major driver of cancer, especially hepatocellular carcinoma (HCC). The prevailing view that non-alcoholic steatohepatitis (NASH) and fibrosis or cirrhosis are required for HCC in obesity. Here, we report NASH obesity can be dissociated. We show the oxidative hepatic environment inactivates STAT-1 STAT-3 phosphatase T cell protein tyrosine (TCPTP) increases signaling. TCPTP deletion hepatocytes promoted recruitment ensuing as well obese C57BL/6 mice normally do not develop HCC....
High-affinity self-reactive thymocytes are purged in the thymus, and residual T cells, which detectable healthy subjects, controlled by peripheral tolerance mechanisms. Breakdown these mechanisms results autoimmune disease, but antigen-specific therapy to augment natural can prevent this. We aimed determine when is most effective. Islet autoantigens, proinsulin (PI), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) were expressed antigen-presenting cells (APCs)...
Abstract Background Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and homeostasis effects prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of bacteria, commonly associated with chronic autoimmune inflammatory diseases, including T1D 2 diabetes. Here, we addressed whether metabolite-based dietary supplement has an impact on humans T1D. We conducted single-arm pilot-and-feasibility trial high-amylose...
OBJECTIVE Chronic exposure of pancreatic β-cells to saturated free fatty acids (FFAs) causes endoplasmic reticulum (ER) stress and apoptosis may contribute β-cell loss in type 2 diabetes. Here, we evaluated the molecular mechanisms involved protection from lipotoxic ER by glucagon-like peptide (GLP)-1 agonists utilized treatment RESEARCH DESIGN AND METHODS INS-1E or fluorescence-activated cell sorter–purified primary rat were exposed oleate palmitate with without GLP-1 agonist exendin-4...
CD4 T-cells secreting interleukin (IL)-17 are implicated in several human autoimmune diseases, but their role type 1 diabetes has not been defined. To address the relevance of such cells, we examined IL-17 secretion response to β-cell autoantigens, IL-17A gene expression islets, and potential functional consequences release for β-cells.Peripheral blood T-cell responses autoantigens (proinsulin, insulinoma-associated protein, GAD65 peptides) were measured by enzyme-linked immunospot assay...
Cytokines produced by islet-infiltrating immune cells induce β-cell apoptosis in type 1 diabetes. The IFN-γ-regulated transcription factors STAT1/IRF-1 have apparently divergent effects on β-cells. Thus, STAT1 promotes and inflammation, whereas IRF-1 down-regulates inflammatory mediators. To understand the molecular basis for these differential outcomes within a single signal transduction pathway, we presently characterized gene networks regulated This was done using siRNA approaches coupled...
Genome-wide association studies allowed the identification of several associations between specific loci and type 1 diabetes (T1D). However, mechanisms by which most candidate genes predispose to T1D remain unclear. We presently evaluated PTPN2, a gene for T1D, modulates β-cell apoptosis after exposure I II interferons (IFNs), cytokines that contribute loss in early T1D.Small interfering RNAs were used inhibit STAT1, Bim, Jun NH(2)-terminal kinase (JNK1) expression. Cell death was assessed...
Environmental factors such as diets rich in saturated fats contribute to dysfunction and death of pancreatic β-cells diabetes. Endoplasmic reticulum (ER) stress is elicited by fatty acids. Here we show that palmitate-induced β-cell apoptosis mediated the intrinsic mitochondrial pathway. By microarray analysis, identified a palmitate-triggered ER gene expression signature induction BH3-only proteins protein 5 (DP5) p53-upregulated modulator (PUMA). Knockdown either reduced cytochrome c...
Apoptosis of pancreatic beta cells is a feature type 2 diabetes and its prevention may have therapeutic benefit. High glucose concentrations induce apoptosis islet cells, this requires the proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins Bim Puma. We studied stress pathways induced by glucotoxicity in that result apoptosis. or ribose increased expression transcription factor CHOP (C/EBP homologous protein) but not endoplasmic reticulum (ER) chaperones, indicating activation ER...
Human islet amyloid polypeptide (hIAPP, or amylin) forms deposits in the islets of Langerhans, a phenomenon that is associated with type-2 diabetes impacting millions people worldwide. Accordingly, strategies against hIAPP aggregation are essential for prevention and eventual treatment disease. Here, it shown generation-3 OH-terminated poly(amidoamine) dendrimer, polymeric nanoparticle, can effectively halt shut down toxicity pancreatic MIN6 NIT-1 cells as well mouse islets. This finding...
Type 1 diabetes is an autoimmune disorder characterized by chronic inflammation and pancreatic beta-cell loss. Here, we demonstrate that the proinflammatory cytokine interleukin-1beta, combined with interferon-gamma, induces expression of Bcl-2 homology 3 (BH3)-only activator PUMA (p53 up-regulated modulator apoptosis) in beta-cells. Transcriptional activation regulated nuclear factor-kappaB endoplasmic reticulum stress but independent p53. leads to mitochondrial Bax translocation,...
Type 1 diabetes is characterized by local inflammation (insulitis) in the pancreatic islets causing β-cell loss. The mitochondrial pathway of apoptosis regulated balance and interaction between Bcl-2 members. Here we clarify molecular mechanism death triggered pro-inflammatory cytokines tumor necrosis factor (TNF)-α interferon (IFN)-γ. combination TNF-α + IFN-γ induced DP5, p53 up-regulated modulator (PUMA), Bim expression human rodent β-cells. DP5 PUMA inactivation RNA interference...
β-Cell destruction in type 1 diabetes (T1D) is at least part consequence of a 'dialog' between β-cells and immune system. This dialog may be affected by the individual's genetic background. We presently evaluated whether modulation MDA5 PTPN2, two candidate genes for T1D, affects β-cell responses to double-stranded RNA (dsRNA), by-product viral replication. These were selected following comparison known T1D expressed pancreatic β-cells, as identified previous array analysis. INS-1E cells...
Tyrosine phosphorylation-dependent signaling, as mediated by members of the epidermal growth factor receptor (EGFR) family (ErbB1 to -4) protein tyrosine kinases (PTKs), Src PTKs (SFKs), and cytokines such interleukin-6 (IL-6) that signal via transducer activator transcription 3 (STAT3), is critical development progression many human breast cancers. EGFR, SFKs, STAT3 can serve substrates for phosphatase TCPTP (PTPN2). Here we report levels are decreased in a subset cancer cell lines vitro...
Human islet amyloid polypeptide (hIAPP or amylin) aggregation is directly associated with pancreatic β-cell death and subsequent insulin deficiency in type 2 diabetes (T2D). Since no cure currently available for T2D, it of great benefit to devise new anti-aggregation molecules, which protect β-cells against hIAPP aggregation-induced toxicity. Engineered nanoparticles have been recently exploited as nanomedicines. In this work, we studied graphene oxide (GO) nanosheets their potential...
Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy against amyloidogenesis to minimize populations toxic oligomers protofibrils by inhibiting protein with small molecules or nanoparticles. However, melanin synthesis in nature realized accelerated fibrillation circumvent accumulation intermediates. Accordingly, we designed demonstrated use star-shaped poly(2-hydroxyethyl acrylate) (PHEA)...
The molecular mechanisms used by olfactory ensheathing cells (OECs) to promote repair in the damaged adult mammalian CNS remain unknown. Thus, we microarrays analyze three OEC populations with different capacities axonal regeneration cultured rat retinal neurons. Gene expression “long-term OECs” that do not stimulate outgrowth was compared of “primary cells” and immortalized cell line TEG3. In this way, identified a number candidate genes might play role promoting regeneration. Among these...
In the course of Type 1 diabetes pro-inflammatory cytokines (e.g., IL-1β, IFN-γ and TNF-α) produced by islet-infiltrating immune cells modify expression key gene networks in β-cells, leading to local inflammation β-cell apoptosis. Most known cytokine-induced transcription factors have pro-apoptotic effects, little is regarding "protective" factors. To this end, we presently evaluated role factor CCAAT/enhancer binding protein delta (C/EBPδ) on apoptosis production inflammatory mediators rat...