A5010970009- Drug Transport and Resistance Mechanisms
- Pediatric Hepatobiliary Diseases and Treatments
- Liver Disease Diagnosis and Treatment
- Liver Diseases and Immunity
- Liver physiology and pathology
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Drug-Induced Hepatotoxicity and Protection
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Liver Disease and Transplantation
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Hepatitis B Virus Studies
- Cystic Fibrosis Research Advances
- Lung Cancer Research Studies
- Cytomegalovirus and herpesvirus research
- ATP Synthase and ATPases Research
- Microtubule and mitosis dynamics
- Gut microbiota and health
- Peptidase Inhibition and Analysis
Charité - Universitätsmedizin Berlin
2020-2025
Massachusetts General Hospital
2023
Centre de Recherche Saint-Antoine
2016-2022
Inserm
2016-2022
Sorbonne Université
2016-2022
Unité de recherche sur les maladies cardiovasculaires et métaboliques
2021
Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal maintain their identity and serve as the body's central bacterial filter. Liver cirrhosis drastically alters vascular architecture, how KCs adapt is unclear. We used a mouse model of fibrosis human tissue examine immune adaptation. Fibrosis forced lose contact with cells, down-regulating "KC identity," which rendered them incapable clearing bacteria. Commensals stimulated recruitment monocytes through...
In liver fibrosis, myofibroblasts derive from HSCs and as yet undefined mesenchymal cells. We aimed to identify portal progenitors of myofibroblasts.Portal cells were isolated mouse bilio-vascular tree analyzed by single-cell RNA-sequencing. Thereby, we uncovered the landscape in homeostatic liver. Trajectory analysis enabled inferring a small cell population further defined surface markers used isolate it. This consisted fibroblasts with stem features (PMSCs), i.e., high clonogenicity...
Background and Aims: Acute liver failure (ALF) is a rare but life-threatening condition, DILI, particularly acetaminophen toxicity, the leading cause of ALF. Innate immune mechanisms further perpetuate injury, while role adaptive system in DILI-related ALF unclear. Approach Results: We analyzed tissue from 2 independent patient cohorts with identified hepatic T cell infiltration as prominent feature human CD8 + cells were characterized by zonation toward necrotic regions an activated gene...
ABCB4 (MDR3) is an adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal absence liver transplantation. In this study, we investigated effect and potential rescue missense variations reside highly conserved...
Technological breakthroughs have fundamentally changed our understanding on the complexity of tumor microenvironment at single-cell level. Characterizing immune cell composition in relation to spatial distribution and histological changes may provide important diagnostic therapeutic information. Immunostaining formalin-fixed paraffin-embedded (FFPE) tissue samples represents a widespread simple procedure, allowing visualization cellular processes, preserved structure. Recent advances...
Immune monitoring of patients on a single-cell level is becoming increasingly important in various diseases. Due to the often very limited availability human specimens and our increased understanding immune systems there an increasing demand analyze as many markers possible simultaneously one panel. Full spectrum flow cytometry emerging powerful tool for since 5-laser instruments enable characterization 40 parameters or more single sample. Nevertheless, even if only machines with fewer...
ABCB4 (ATP-binding cassette subfamily B member 4) is a hepatocanalicular floppase involved in biliary phosphatidylcholine (PC) secretion. Variations the gene give rise to several diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), an autosomal recessive disease that can be lethal absence of liver transplantation. In this study, we investigated effect and potential rescue ten missense variations NBD1:NBD2 homologous positions (Y403H/Y1043H, K435M/K1075M,...
Abstract Adenosine triphosphate binding cassette transporter, subfamily B member 4 (ABCB4) is the transporter of phosphatidylcholine at canalicular membrane hepatocytes. ABCB4 deficiency, due to genetic variations, responsible for progressive familial intrahepatic cholestasis type 3 (PFIC3) and other rare biliary diseases. Roscovitine a molecule in clinical trial that was shown correct F508del variant cystic fibrosis transmembrane conductance regulator (CFTR), another ABC transporter. In...
Abstract The gut‐liver axis includes the bidirectional communication between gut and liver, thus covers signals from liver‐to‐gut gut‐to‐liver. Disruptions of have been associated with progression chronic liver diseases, including alcohol‐related metabolic dysfunction‐associated steatotic disease cholangiopathies. Immune cells their expression pattern recognition receptors, activation markers or immune checkpoints might play an active role in liver. Here, we present a 26‐color full spectrum...
ABCB4 is expressed at the canalicular membrane of hepatocytes. This ATP-binding cassette (ABC) transporter responsible for secretion phosphatidylcholine into bile canaliculi. Missense genetic variations are correlated with several rare cholestatic liver diseases, most severe being progressive familial intrahepatic cholestasis type 3 (PFIC3). In a repurposing strategy to correct intracellularly retained variants, we tested 16 compounds previously validated as cystic fibrosis transmembrane...
Ferroptosis is a recently recognized iron-dependent form of non-apoptotic regulated cell death (RCD) characterized by lipid peroxide accumulation to lethal levels. Cancer cells, which show an increased iron dependency enable rapid growth, seem vulnerable ferroptosis. There also increasing evidence that ferroptosis might be immunogenic and therefore could synergize with immunotherapies. Hepatocellular carcinoma (HCC) the most common primary liver tumor low survival rate due frequent...
Clinical management of gastroenteropancreatic neuroendocrine neoplasms remains challenging. We recently introduced the FMS-like tyrosine kinase 3 ligand (FLT3LG) as a possible biomarker for proinflammatory tumor microenvironment. Here, we put spotlight on quantitative assessment classical dendritic cells (cDC) and T in context FLT3LG mRNA levels retrospective study (NET) G2/G3 carcinoma (NEC) pancreatic gastric origin. The abundance cDC their relevant subpopulations were determined by...
ABCB4, is an adenosine triphosphate-binding cassette (ABC) transporter localized at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine secretion into bile. Gene variations ABCB4 cause different types liver diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3). The molecular mechanisms underlying trafficking to and from are still unknown. We identified serine/threonine kinase Myotonic dystrophy kinase-related Cdc42-binding isoform α...
ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations are associated with several rare cholestatic diseases. The available treatments not efficient for a significant proportion patients ABCB4-related diseases and liver transplantation often required. development novel therapies requires deep understanding molecular mechanisms regulating...
Although inflammation appears to be a driver of cholestatic liver disease progression, the exact mechanisms linking biliary injury, and fibrosis remain poorly understood. Remarkable changes in composition gut microbiota patients with primary sclerosing cholangitis (PSC) other diseases suggest have been reported, suggesting that dysbiosis may crucial for cholangiopathy pathogenesis or progression. Moreover, approximately 80% PSC suffer from inflammatory bowel disease. In this study, using...