A5068899322- Liver physiology and pathology
- Pluripotent Stem Cells Research
- Renal and related cancers
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Telomeres, Telomerase, and Senescence
- Organ Transplantation Techniques and Outcomes
- T-cell and B-cell Immunology
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Immunotherapy and Immune Responses
- Mesenchymal stem cell research
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- NF-κB Signaling Pathways
- Congenital heart defects research
- Neonatal Respiratory Health Research
- Pancreatic and Hepatic Oncology Research
- Cardiac Fibrosis and Remodeling
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Inflammasome and immune disorders
- Genomics, phytochemicals, and oxidative stress
- Myasthenia Gravis and Thymoma
AstraZeneca (United Kingdom)
2020-2022
Candiolo Cancer Institute
2022
Istituti di Ricovero e Cura a Carattere Scientifico
2022
King's College London
2018-2020
University of Cagliari
1972-2020
Boston University
2012-2018
Boston Medical Center
2012-2018
Universitat de Barcelona
1997-2013
Institute for Research in Biomedicine
2007-2011
Harvard University
2011
Abstract Hepatocyte transplantation to treat liver disease is largely limited by the availability of useful cells. Human amniotic epithelial cells (hAECs) from term placenta express surface markers and gene characteristics embryonic stem have ability differentiate into all three germ layers, including tissues endodermal origin (i.e., liver). Thus, hAECs could provide a source cell–derived hepatocytes for transplantation. We investigated differentiation in vitro after livers severe combined...
MicroRNA–protein complexes (microRNPs) can activate translation of target reporters and specific mRNAs in quiescent (i.e., G0) mammalian cell lines. Induced cells, like folliculated immature oocytes, have high levels cAMP that protein kinase AII (PKAII) to maintain G0 states. We report microRNA-mediated up-regulated expression Xenopus laevis dependent on AGO or human AGO2 FXR1, as cells. Importantly, we find maintenance downstream PKAII signaling are required for oocytes. identify an...
Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized lines resultant structures that are difficult to control or scale. To address these challenges, we aimed develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose...
Abstract The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin human parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report existence a hepatobiliary hybrid progenitor (HHyP) population in foetal using single-cell RNA sequencing. HHyPs are anatomically restricted to ductal plate maintain transcriptional profile distinct from hepatocytes, mature BECs. In addition,...
The in vitro directed differentiation of pluripotent stem cells (PSCs) through stimulation developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or regenerative therapies. However, there has been significant uncertainty regarding how to separately derive lung vs. thyroid epithelial lineages, since these two each originate from Nkx2-1+ foregut progenitors, and the minimal claimed regulate their distinct lineage specification vivo have varied...
A new tissue sample embedding and processing method is presented that provides downstream compatibility with numerous different histological, molecular biology, analytical techniques. The methodology based on the low temperature of fresh frozen specimens into a hydrogel matrix composed hydroxypropyl methylcellulose (HPMC) polyvinylpyrrolidone (PVP) sectioning using cryomicrotome. was expected not to interfere standard characterization methods, histologically or analytically. We assessed this...
Osteochondral defects remain a major clinical challenge mainly due to the combined damage articular cartilage and underlying bone, interface between two tissues having very different properties. Current treatment modalities have several limitations drawbacks, with limited capacity of restoration; however, tissue engineering shows promise in improving outcomes osteochondral defects. In this study, novel gradient scaffold has been fabricated, implementing structure design mimic anatomical,...
Abstract Although reprogramming of cellular metabolism is a hallmark cancer, little known about how metabolic contributes to early stages transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss results in an increase number stem cells (ISCs), which translates into enhanced initiating potential APC min mice. By tracking down connection between and initiation, find compartmentalization within...
Gemcitabine (dFdC) is a common treatment for pancreatic cancer; however, it thought that may fail because tumor stroma prevents drug distribution to cells. pro-drug with active metabolites generated intracellularly; therefore, visualizing the of parent as well its important. A multimodal imaging approach was developed using spatially coregistered mass spectrometry (MSI), cytometry (IMC), multiplex immunofluorescence microscopy (mIF), and hematoxylin eosin (H&E) staining assess local...
Abstract Macrophages are an essential component of both innate and adaptive immunity, altered function these cells with aging may play a key role in immunosenescence. To determine the effect on macrophages, we produced bone marrow-derived macrophages vitro. In conditions, analyzed without influence other cell types that be affected by aging. We showed telomeres shorten age leading to decreased GM-CSF but not M-CSF-dependent proliferation as result phosphorylation STAT5a. from aged mice...
α1-Antitrypsin deficiency (A1ATD) is an autosomal recessive disorder caused by mutations in the SERPINA1 gene. Individuals with Z variant (Gly342Lys) retain polymerised protein endoplasmic reticulum (ER) of their hepatocytes, predisposing them to liver disease. The concomitant lack circulating A1AT also causes lung emphysema. Greater insight into mechanisms that link misfolding injury will facilitate design novel therapies.Human-induced pluripotent stem cell (hiPSC)-derived hepatocytes...
The three-prime repair exonuclease 1 (TREX1) is the most abundant in mammalian cells. Mutations Trex1 gene are being linked to development of Aicardi-Goutières syndrome, an inflammatory disease brain, and systemic lupus erythematosus. In clinical cases a Trex1-deficient murine model, chronic production type I IFN plays pathogenic role. this study, we demonstrate that Trex1(-/-) mice present signatures many different organs, including brain. highly induced macrophages response proinflammatory...
TREX1 is the most abundant mammalian 3′ → 5′ DNA exonuclease. It has been described to form part of SET complex and responsible for Aicardi-Goutières syndrome in humans. Here we show that exonuclease activity correlated binding preferences toward certain sequences. In particular, have found three motifs are selected, GAG, ACA, CTGC. To elucidate how discrimination occurs, determined crystal structures two murine complexes, with a nucleotide product reaction, single-stranded substrate. Using...
Abstract After interaction with its receptor, GM-CSF induces phosphorylation of the β-chain in two distinct domains macrophages. One activation mitogen-activated protein kinases and PI3K/Akt pathway, other JAK2-STAT5. In this study we describe how trichostatin A (TSA), which inhibits deacetylase activity, blocks JAK2-STAT5-dependent gene expression but not genes that depend on signal transduction induced by domain receptor. TSA treatment inhibited GM-CSF-dependent proliferation macrophages...
Abstract MAPK phosphatase‐1 (MKP‐1) is a protein phosphatase that plays crucial role in innate immunity. This inactivates ERK1/2, which are involved two opposite functional activities of the macrophage, namely proliferation and activation. Here we found although macrophage activation induce MKP‐1 with different kinetics, gene expression mediated by proximal promoter sequences localized between −380 −180 bp. Mutagenesis experiments element determined CRE/AP‐1 required for LPS‐ or...
The expression of MHC class II genes is strictly tissue specific. In a limited number cells, the these inducible by cytokines and only in dendritic B cells constitutive. LPS blocks cytokine-dependent induction genes, but enhances their cell line A20. We have observed that increased surface raising I-A protein mRNA levels. does not enhance transactivator CIITA. transient transfection experiments, induced I-Abeta promoter, which contains an AP-1 box located between 1722 1729 bp upstream...
A better understanding of the complex relationship between aging and cancer will provide important tools for prevention treatment neoplasia. In these studies, hypothesis was tested that may fuel carcinogenesis via alterations imposed in tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats their fate followed over time using dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells....
The expressions of CNT and ENT (concentrative equilibrative nucleoside transporters) in macrophages are differentially regulated by IFN-gamma (interferon-gamma). This cytokine controls gene expression through STAT1-dependent and/or -independent pathways (where STAT1 stands for signal transduction activator transcription 1). In the present study, role response transporters to was studied using from knockout mice. triggered an inhibition ENT1-related transport activity mechanisms. Such...
In the retrorsine (RS)-based model of massive liver repopulation, preexposure to this naturally occurring alkaloid is sufficient prime normal host parenchymal cells be slowly replaced by transplanted hepatocytes. The basis for striking effect yet fully elucidated. present studies possible involvement cell senescence was investigated. Fischer 344 rats were treated according RS-based protocol hepatocyte transplantation, i.e., two doses RS, 2 weeks apart, and killed at 4 or 8 after treatment....