A5058523274- Liver physiology and pathology
- Prostate Cancer Treatment and Research
- Liver Disease Diagnosis and Treatment
- Prostate Cancer Diagnosis and Treatment
- Pancreatic function and diabetes
- Organ Transplantation Techniques and Outcomes
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- Growth Hormone and Insulin-like Growth Factors
- Virus-based gene therapy research
- FOXO transcription factor regulation
- Lysosomal Storage Disorders Research
- Immunotherapy and Immune Responses
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Cancer, Lipids, and Metabolism
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Autism Spectrum Disorder Research
- Urologic and reproductive health conditions
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- CRISPR and Genetic Engineering
Université Paris Cité
2013-2023
Centre National de la Recherche Scientifique
2005-2023
Inserm
2013-2023
Institut Necker Enfants Malades
2014-2023
Délégation Paris 5
2007-2019
Sorbonne Paris Cité
2013-2017
Institut Cochin
2002-2016
Institut Curie
2016
Sorbonne Université
2016
Foie, Métabolisme, Cancer
2010
Polyploidy is a general physiological process indicative of terminal differentiation. During liver growth, this generates the appearance tetraploid (4n) and octoploid (8n) hepatocytes with one or two nuclei. The onset polyploidy in has been recognized for quite some time; however, cellular mechanisms that govern it remain unknown. In report, we observed sequential during growth binuclear diploid (2 x 2n) mononuclear 4n from hepatocyte population. To identify cell cycle modifications involved...
Muscle fibers show great differences in their contractile and metabolic properties. This diversity enables skeletal muscles to fulfill adapt different tasks. In this report, we that the Six/Eya pathway is implicated establishment maintenance of fast-twitch muscle phenotype. We demonstrate MEF3/Six DNA binding element present aldolase A pM promoter mediates high level activation glycolytic (but not slow-twitch) fibers. also among Six Eya gene products expressed mouse muscle, Six1 Eya1...
Loss of normal primary cilia function in mammals is linked to proliferative diseases, such as polycystic kidney disease, suggesting a regulatory relationship between and cell cycle. The cilium expressed by most mammalian cells nucleated from the elder centriole centrosome. centrosome suggests that these structures share functions components. We now show IFT88/polaris, component intraflagellar transport, remains associated state. IFT88/polaris tightly with throughout cycle microtubule-...
Cell-based therapy may some day be a therapeutic alternative to liver transplantation. Recent observations indicating that hematopoietic stem cells can differentiate into hepatocytes have opened new prospects. However, the clinical relevance of this phenomenon is unknown. We previously developed strategy based on protective effect Bcl-2 against Fas-mediated apoptosis selectively amplify small number in vivo. now show approach used minor population bone marrow-derived hepatocytes. Normal mice...
A critical knowledge gap in prostate cancer research is understanding whether castration-tolerant progenitor-like cells that reside treatment-naive tumors play a direct role therapy resistance and tumor progression. Herein, we reveal the castration tolerance of LSCmed (Lin-, Sca-1+, CD49fmed) progenitor cells, mouse equivalent human prostatic Club arises not from intrinsic properties but significant transcriptional reprogramming. Utilizing single-cell RNA sequencing isolated...
GH is a pleiotropic hormone that plays major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was identify by which controls regeneration. We performed two thirds partial hepatectomies receptor (GHR)-deficient mice wild-type littermates showed blunted progression G1/S transition...
GH pathway has been shown to play a major role in liver regeneration through the control of epidermal growth factor receptor (EGFR) activation. This is down-regulated nonalcoholic fatty disease. Because known be impaired livers, we wondered whether deregulation GH/EGFR could explain this deficiency. Hepatic EGFR expression and triglyceride levels were quantified biopsies 32 obese patients with different degrees steatosis. We showed significant inverse correlation between level hepatic...
The severe neurodegenerative disorder, Tays-Sachs disease, is caused by a beta-hexosaminidase alpha-subunit deficiency which prevents the formation of lysosomal heterodimeric alpha-beta enzyme, hexosaminidase A (HexA). No treatment available for this fatal disease; however, gene therapy could represent therapeutic approach. We previously have constructed and characterized, in vitro, adenoviral retroviral vectors coding alpha- beta-subunits human beta-hexosaminidases. Here, we determined vivo...
It has been suggested that increasing age is correlated with an acceleration of the progression liver fibrosis induced by various agents, such as hepatitis C virus or chronic alcohol consumption. However, cellular and molecular changes underlying this predisposition are not entirely understood. In context aging population, it becomes challenging to decipher mechanisms responsible for higher susceptibility older individuals acquired disorder. To address issue, we carbon tetrachloride (CCl(4))...
Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen deprivation remain poorly described, despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild-type (WT) mouse prostates rare population luminal progenitor cells we called LSCmed according their FACS profile (Lin- /Sca-1+ /CD49fmed ). Here, investigated prevalence and castration resistance models tumourigenesis (Pb-PRL, Ptenpc-/- , Hi-Myc...
Unraveling the molecular clues of liver proliferation has become conceivable thanks to model two-third hepatectomy. The synchronicity and well-scheduled aspect this process allow scientists slowly decipher mystery. During phenomenon, quiescent hepatocytes remnant lobes are able reenter into cell cycle initiating G1-S progression synchronously before completing cycle. major role played by step been emphasized loss-of-function studies showing a delay or lack coordination in progression. Two...
Allogenic hepatocyte transplantation or autologous of genetically modified hepatocytes has been used successfully to correct congenital acquired liver diseases and can be considered as an alternative orthotopic transplantation. However, are neither easily maintained in culture nor efficiently very sensitive dissociation before their reimplantation into the recipient. These difficulties have greatly limited use ex vivo approach clinical trials. In present study, we shown that primary human...
Background: The molecular and cellular mechanisms that drive castration-resistant prostate cancer (CRPC) remain poorly understood. LSCmed cells defines an FACS-enriched population of castration-tolerant luminal progenitor has been proposed to promote tumorigenesis CRPC in Pten-deficient mice. goals this study were assess the relevance through analysis their proximity with progenitor-like cell clusters identified by single-cell (sc)RNA-seq analyses mouse human prostates, investigate...
The canonical prolactin (PRL) Signal Transducer and Activator of Transcription (STAT) 5 pathway has been suggested to contribute human prostate tumorigenesis via an autocrine/paracrine mechanism. probasin (Pb)-PRL transgenic mouse models this mechanism by overexpressing PRL specifically in the epithelium leading strong STAT5 activation luminal cells. These mice exhibit hypertrophic prostates harboring various pre-neoplastic lesions that aggravate with age accumulation castration-resistant...
New predictive biomarkers are needed to accurately predict metastasis-free survival (MFS) and cancer-specific (CSS) in localized prostate cancer (PC). Keratin-7 (KRT7) overexpression has been associated with poor prognosis several cancers is described as a novel progenitor marker the mouse prostate.KRT7 expression was evaluated prostatic cell lines human tissue by immunohistochemistry (IHC, on advanced PC, n = 91) immunofluorescence (IF, 285). The KRT7 mean fluorescence intensity (MFI)...
Orthotopic liver transplantation is limited by the shortage of donors, leading to elderly patients being enrolled as donors with increasing frequency. Alternative strategies such cell therapy are therefore needed. Because transplanted hepatocytes do not proliferate into a recipient liver, repopulation have been developed. We previously published proof concept that harboring survival selective advantage can efficiently repopulate mouse liver. develop here an alternative approach conferring...
In a cohort of 95 women with multiple breast fibroadenomas (MFAs), we recently identified patients harboring germline heterozygous variants the prolactin receptor (PRLR) exhibiting constitutive activity (PRLRI146L and PRLRI176V).This study sought to better delineate potential role PRLR gain-of-function in benign malignant mammary tumorigenesis.This was an observational transgenic mouse model analysis.The took place at Department Endocrinology, Reproductive Disorders Rare Gynecologic...