A5087684079- Cell death mechanisms and regulation
- Ion Channels and Receptors
- Phagocytosis and Immune Regulation
- Pregnancy and Medication Impact
- interferon and immune responses
- Neurobiology and Insect Physiology Research
- Autophagy in Disease and Therapy
- Toxin Mechanisms and Immunotoxins
- Birth, Development, and Health
- Heat shock proteins research
- Connexins and lens biology
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- RNA Interference and Gene Delivery
- Phytochemicals and Antioxidant Activities
- Inflammasome and immune disorders
- Sexual Differentiation and Disorders
- Calpain Protease Function and Regulation
- Natural Antidiabetic Agents Studies
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects of Natural Compounds
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Ocular Oncology and Treatments
Université de Poitiers
2020-2024
Centre National de la Recherche Scientifique
2020-2024
Inserm
2000-2022
Institut de Recherche en Santé, Environnement et Travail
2017-2022
École des Hautes Études en Santé Publique
2018-2022
Université de Rennes
2017-2022
Cancers et Préventions
2021
MRC Centre for Reproductive Health
2018
The Queen's Medical Research Institute
2018
University of Edinburgh
2018
Fas-associated death domain protein (FADD) and caspase-8 (casp8) are vital intermediaries in apoptotic signaling induced by tumor necrosis factor family ligands. Paradoxically, lymphocytes lacking FADD or casp8 fail to undergo normal clonal expansion following antigen receptor cross-linking succumb caspase-independent cell upon activation. Here we show that T cells activity subject hyperactive autophagic subvert a cellular survival mechanism into potent process. autophagy, enhanced mitogenic...
Melanoma is a highly aggressive cancer endowed with unique capacity of rapidly metastasizing, which fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination melanoma cells during metastasis, therefore primary importance. Here, we uncover the prominent expression plasma membrane TRPV2 calcium channel as distinctive feature tumors, directly related to metastatic dissemination. In vitro well in vivo,...
Abstract Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection inflammatory diseases). driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) RIPK3, pseudo-kinase MLKL (Mixed Lineage domain-Like) associated multi-protein complex called necrosome. In order find new inhibitors for use human therapy, chemical...
Does ibuprofen use during the first trimester of pregnancy interfere with development human fetal ovary?In fetuses, exposure is deleterious for ovarian germ cells.In utero stages define future reproductive capacity a woman. In rodents, analgesics can impair ovary leading to early onset fertility failure. Ibuprofen, which available over-the-counter, has been reported as frequently consumed medication pregnancy, especially when cells undergo crucial steps proliferation and...
In contrast with protein kinase Calpha (PKCalpha) and PKCepsilon, which are better known for promoting cell survival, PKCdelta is its pro-apoptotic function, exerted mainly through a caspase-3-dependent proteolytic activation pathway. the present study, we used rat GH3B6 pituitary adenoma line to show that PKCalpha PKCepsilon activated relocalized together when apoptosis induced by genotoxic stress. Proteolytic crucial step three isoforms since: (1) catalytic domains of PKCalpha, or...
Ca2+ influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here, we show that inhibition of channel activity increases average velocities by reducing the frequency pauses human cells migrating confined spaces, even absence extrinsic contacts or antigen recognition. Utilizing novel ratiometric genetically encoded cytosolic indicator, Salsa6f, which permits real-time monitoring along with motility,...
Necroptosis is a regulated form of cell death involved in several disease models including particular liver diseases. Receptor‐interacting protein kinases, RIPK 1 and 3, are the main serine/threonine kinases driving this pathway. We screened noncommercial, kinase‐focused chemical library which allowed us to identify Sibiriline as new inhibitor necroptosis induced by tumor necrosis factor ( TNF ) Fas‐associated with domain FADD )‐deficient Jurkat cells. Moreover, Sib inhibits necroptotic...
Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis ovary development humans?The characterization of a dynamically regulated protein-coding non-coding landscape developing human both sexes highlights large number potential key regulators that show an early sexually dimorphic expression pattern.Gonadal is orchestrated by gene XX XY gonads. A comprehensive its counterpart offers promising perspectives for...
Abstract Fas-associated death domain protein (FADD) constitutes an essential component of TNFR-induced apoptotic signaling. Paradoxically, FADD has also been shown to be crucial for lymphocyte development and activation. In this study, we report that is necessary long-term maintenance S6 kinase (S6K) activity. phosphorylation at serines 240 244 was only observed after stimulation wild-type cells, roughly corresponding the time before S-phase entry, poorly induced in T cells expressing a...
Abstract In T lymphocytes, Ca2+ release–activated (CRAC) channels composed of Orai1 subunits trigger Ag-induced gene expression and cell proliferation through the NFAT pathway. We evaluated requirement CRAC channel function for lymphocyte homing using a dominant-negative Orai1-E106A mutant to suppress signaling. To investigate motility human lymphocytes in immunocompromised mouse hosts, we transferred either acutely or after stable engraftment second transfer from same blood donor. Human was...
Abstract DRAK2 is a serine/threonine kinase highly enriched in lymphocytes that raises the threshold for T cell activation and maintains survival following productive activation. cells lacking are prone to under suboptimal conditions exhibit enhanced calcium responses AgR stimulation. Despite this, mice resistant organ-specific autoimmune diseases due defective autoreactive survival. activity induced by signaling, this study we show induction of requires Ca2+ influx through release-activated...
Acetaminophen (APAP, paracetamol) is widely used by pregnant women. Although long considered safe, growing evidence indicates that APAP an endocrine disruptor since in utero exposure may be associated with a higher risk of male genital tract abnormalities. In rodents, fetal has long-term effects on the reproductive function female offspring. Human studies have also suggested harmful effects.Given disruption ovarian development impact women's health, we investigated human ovaries...
The GAGA box of the rat serine protease inhibitor 2 (spi 2) genes not only acts as a basal promoter element, but also mediates transcriptional activation by growth hormone and interleukin-6. is separated from TATA 12 bp, this close association required for efficient transcription. Hence, may influence transcription efficiency through interactions between binding proteins some components RNA polymerase II complex. Here we report cloning two box-binding termed p38 p40, that belong to type A/B...
The BCL-2 family protein BAK is a key regulator of mitochondrial apoptosis. activation first involves N-terminal conformational changes that lead to the transient exposure BH3 domain then inserts into hydrophobic groove on another molecule form symmetric dimers. We showed recently post-translational modifications are important in regulation change and multimerization, with dephosphorylation at tyrosine 108 constituting an initial step process. now show serine 117 (S117), located groove, also...
Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid from fifth month of gestation. The nephrotoxicity these three is well documented in adults, as their interference with prostaglandins biosynthesis. Here we investigated effect on human first trimester kidneys ex vivo. We evaluated biosynthesis functionality performing a wide screening prostaglandin expression patterns kidneys. demonstrated that machinery...
ABSTRACT Despite being considered a rare tumor, uveal melanoma (UVM) is the most common adult intraocular malignancy. With poor prognosis and limited treatment options, up to 50% of patients develop metastases, primarily in liver. A range mutations chromosomal aberrations with significant prognostic value has been associated UVM pathogenesis. The frequently mutated genes are GNAQ GNA11, which encode α subunits Gq proteins described as driver that activate multiple signaling cascades involved...
(Abstracted from Hum Reprod 2018;33(3):482–493) Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used over-the-counter medications for treatment pain, inflammation, and fever. In 2013, up to 28.3% pregnant women reported use ibuprofen at some stage during their pregnancy.
Abstract In T lymphocytes, Ca2+ release-activated (CRAC) channels composed of Orai1 subunits trigger antigen-induced gene expression through the NFAT pathway. Lymphocyte homing into lymph nodes may also require CRAC channel function. We evaluated requirements for human lymphocyte homing, using a dominant-negative Orai1-E106A mutant to suppress signaling. To investigate and motility lymphocytes we transferred cells immunocompromised mouse hosts following stable reconstitution. Human was...
Abstract Apoptosis and autophagy are critical mediators of a functional immune response. FADD caspase-8 (casp8) were originally discovered to transduce apoptotic signals delivered through TNF family members. Paradoxically, lymphocytes lacking or casp8 function have impaired clonal expansion following antigen receptor crosslinking succumb caspase-independent cell death. We show that T cells subject hyperactive autophagy. induces activation its interaction with FADD:Atg5:Atg12 complexes....
Abstract FADD constitutes an essential component of TNF receptor-induced apoptotic signaling. Paradoxically, has also been shown to be crucial for lymphocyte development and activation. Using mice expressing a T cell specific transgene encoding the death domain (FADDdd), we have found that participates in clonal expansion. Based on BrdU uptake assays, signaling is required transition between late G1 S-phase cycle. The defective progression through cycle marked by defect cyclin E expression...