A5066407367- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Autoimmune and Inflammatory Disorders Research
- Pancreatic function and diabetes
- CAR-T cell therapy research
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Protein purification and stability
- Lymphoma Diagnosis and Treatment
- NF-κB Signaling Pathways
- Transgenic Plants and Applications
- Viral-associated cancers and disorders
- Signaling Pathways in Disease
- Biosimilars and Bioanalytical Methods
- Diabetes and associated disorders
- Receptor Mechanisms and Signaling
- Blood disorders and treatments
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Pancreatitis Pathology and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
BD Biosciences (United States)
2021
Torrey Pines Institute For Molecular Studies
2021
Scripps Research Institute
2011-2016
Université Paris Cité
2006-2014
Inserm
2007-2014
Sorbonne Paris Cité
2014
Délégation Paris 5
2006-2011
Institut Necker Enfants Malades
2007-2011
Hôpital Necker-Enfants Malades
2007-2011
Modèles Insectes de l'Immunité Innée
2006
Studies of knockout mice delineate specific and overlapping roles for different protein kinase C isoforms in T cell biology.
An allelic variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22), PTPN22R620W, is strongly associated with 1 diabetes (T1D) in humans and increases the risk T1D by two- to fourfold. The NOD mouse a spontaneous model that shares many genetic pathways contributing T1D. We hypothesized introduction murine orthologous Ptpn22R619W mutation genome would enhance development microinjected CRISPR-Cas9 homology-directed repair template into single-cell zygotes introduce its endogenous...
β-selection is the most pivotal event determining αβ T cell fate. Here, surface-expression of a pre-T receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. Besides pre-TCR, also requires co-stimulatory signals from Notch receptors - key fate determinants in eukaryotes. we show that this Notch-dependence established through antagonistic signaling by pre-TCR/Notch effector, phosphoinositide 3-kinase (PI3K), inositol-trisphosphate B (Itpkb)....
Mutations in the X-linked inhibitor of apoptosis (XIAP) gene have been associated with XLP-like disease, including recurrent Epstein-Barr virus (EBV)-related haemophagocytic lymphohystiocytosis (HLH), but immunopathogenic bases EBV-related disease XIAP deficiency is unknown. We present first analysis EBV-specific T cell responses functional deficiency. In a family patients novel mutation (G466X) leading to late-truncated protein and varying clinical features, we identified gradual...
The inositol-phosphate messenger inositol(1,3,4,5)tetrakisphosphate (IP4) is essential for thymocyte positive selection by regulating plasma-membrane association of the protein tyrosine kinase Itk downstream T cell receptor (TCR). IP4 can act as a soluble analog phosphoinositide 3-kinase (PI3K) membrane lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3). PIP3 recruits signaling proteins such to cellular membranes binding PH and other domains. In thymocytes, low-dose domain...
Binding of the membrane phospholipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) to Pleckstrin Homology (PH) domain Tec family protein tyrosine kinase, Inducible T cell Kinase (ITK), is critical for recruitment kinase plasma and its co-localization with TCR-CD3 molecular complex. Three aromatic residues, termed FYF motif, located in inner walls phospholipid-binding pocket ITK PH domain, are conserved domains all kinases, but not other PH-domain containing proteins, suggesting an...
The inositol-phosphate messenger inositol (1,3,4,5)tetrakisphosphate (IP 4 ) is essential for thymocyte positive selection by regulating plasma-membrane association of the protein tyrosine kinase Itk downstream T cell receptor (TCR).IP can act as a soluble analog phosphoinositide 3-kinase (PI3K) membrane lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP 3 ).PIP recruits signaling proteins such to cellular membranes binding PH and other domains.In thymocytes, low-dose IP domain...
> L’homeostasie des lymphocytes au cours de la reponse immunitaire est un mecanisme soumis a une regulation fine. C’est equilibre permanent entre proliferation cellules activees et leur apoptose (ou mort cellulaire programmee). Chez l’homme, defauts l’homeostasie lymphocytaire peuvent conduire nombreuses maladies comme les lymphomes, syndromes d’activation macrophagique syndrome hemophagocytaire) ou auto-immunes. Le Purtilo, lymphoproliferatif lie l’X (XLP), immunodeficience primaire rare,...
Abstract Accounting for ~4% of all cancers in the US, Non-Hodgkin Lymphoma (NHL) is most prevalent blood cancer. Diffuse large B-cell (DLBCL) common and aggressive type NHL. Here, we identify inositol-trisphosphate (IP3) 3-kinase B (Itpkb) as a novel tumor suppressor whose deficiency triggers DLBCL mice. We found that aging Itpkb−/− mice die prematurely with anemia splenomegaly. 15% these showed multiorgan-infiltration neoplastic germinal-center phenotype cells reminiscent DLBCL. Itpkb−/−B...
Abstract Each chain of the αβ T-cell receptor (TCR) contains a constant (C) region and an antigen-binding variable (V) region. There are two human isoforms TCR β chain, TRBC1 TRBC2, differing slightly in region, individual T-cells express one isoform or other. The ratio TRBC1+ to TRBC2+ falls within characteristic range healthy donors; monoclonal malignancies skew this dramatically. A antibody specific for (clone JOVI.1) is unable directly identify both T cell as done B cancers using k...
Abstract Biosimilars for therapeutic antibodies contain identical variable sequences to FDA-approved antibodies. Recombinant BD research-grade biosimilars can be used model several important aspects of major antibody therapies in use today. Our with the huIgG1 (N297A) Fc mutation exhibit greatly reduced background binding and clarify identification/study target cell subsets. These flow cytometry reagents are available many fluorochrome options facilitate deeper phenotyping using large...
NK cells are important for cancer immunosurveillance, bone marrow allograft rejection, fighting infections and reproduction. Overcoming their limited efficacy in immunotherapies requires a better understanding of the mechanisms limiting cell effector functions. recognize kill pathogen‐infected or tumor through receptors (NKR). Two second‐messenger downstream pathways required maturation function: PIP3‐generation by PI3K, generation DAG IP3 PLCγ. has key signaling role mobilizing Calcium, but...
Abstract NK cells have important functions in cancer immunosurveillance, BM allograft rejection, fighting infections and reproduction. cell-based therapies are promising blood treatments. Overcoming their limited efficacy requires a better understanding of the molecular mechanisms dampening effector functions. recognize kill pathogen-infected or tumor through invariant cell receptors (NKR). Two second-messenger pathways downstream NKRs required for maturation responses: PIP3-generation by...
Abstract In β-selection, surface-expression of a pre-T cell receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. This pivotal αβ T fate-determining event requires co-stimulatory Notch signals. Here, we show that this dependence is enforced through antagonistic signaling by inositol-trisphosphate 3-kinase B (Itpkb) phosphoinositide (PI3K). Itpkb produces soluble inositol-tetrakisphosphate which competes with the PI3K lipid-product PIP3 for...
Abstract Accounting for ∼4% of all cancers in the US, Non-Hodgkin Lymphoma (NHL) is most prevalent blood cancer. Diffuse large B-cell (DLBCL) common and aggressive type NHL. Here, we identify inositol-trisphosphate (IP3) 3-kinase B (Itpkb) as a novel tumor suppressor whose deficiency triggers DLBCL mice. We found that aging Itpkb-/- mice die prematurely with anemia splenomegaly. 15% these showed multiorgan-infiltration neoplastic germinal-center phenotype cells reminiscent DLBCL. cell...
Abstract Tight regulation of HSC homeostasis ensures life-long hematopoiesis and prevents blood cancers. The mechanisms balancing quiescence with expansion differentiation into hematopoietic progenitors are incompletely understood. Here, we identify inositoltrisphosphate (IP3) 3-kinase B (Itpkb) as a novel essential regulator function. Young Itpkb-/- mice accumulated phenotypic which were less quiescent proliferated more than wildtype controls. downregulated associated mRNAs, but upregulated...
Abstract In β-selection, surface-expression of a pre-T cell receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. This pivotal αβ T fate-determining event requires co-stimulatory Notch signals. Here, we show that this dependence is enforced through antagonistic signaling by inositol-trisphosphate 3-kinase B (Itpkb) phosphoinositide (PI3K). Itpkb produces soluble inositol-tetrakisphosphate which competes with the PI3K lipid-product PIP3 for...