- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- Angiogenesis and VEGF in Cancer
- Fluorine in Organic Chemistry
- Retinopathy of Prematurity Studies
- Corneal surgery and disorders
- Corneal Surgery and Treatments
- Biomarkers in Disease Mechanisms
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Folate and B Vitamins Research
- Connective Tissue Growth Factor Research
- Adenosine and Purinergic Signaling
- Axon Guidance and Neuronal Signaling
- CAR-T cell therapy research
- Pneumocystis jirovecii pneumonia detection and treatment
- HIV/AIDS drug development and treatment
- Apelin-related biomedical research
- T-cell and B-cell Immunology
Inserm
2019-2024
Université Paris Cité
2019-2024
Institut des Maladies Génétiques Imagine
2019-2024
Sorbonne Paris Cité
2019-2020
Paris Biotech Santé
2014
Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of on vascular smooth muscle (VSMC) activity vitroand vivo. show exogenous stimulated VSMC adhesion migration, increased their coverage EC tubes (grown a Matrigel substrate). siRNA knock-down endogenous expression decreased recruitment to tubes. expressed three...
Cytidine triphosphate (CTP) synthetase 1 (CTPS1) deficiency is caused by a unique homozygous frameshift splice mutation (c.1692-1G>C, p.T566Dfs26X). CTPS1-deficient patients display severe bacterial and viral infections. CTPS1 responsible for CTP nucleotide de novo production involved in DNA/RNA synthesis. Herein, we characterized depth lymphocyte defects associated with deficiency. Immune phenotyping performed 7 showed absence or low numbers of mucosal-associated T cells, invariant NKT...
The CTP nucleotide is a key precursor of nucleic acids metabolism essential for DNA replication. De novo production relies on synthetases 1 and 2 (CTPS1 CTPS2) that catalyze the conversion UTP into CTP. synthetase activity high in proliferating cells including cancer cells; however, respective roles CTPS1 CTPS2 cell proliferation are not known. By inactivation
Lymphoma is the most common hematological malignancy and among 10 prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes rate-limiting step in pyrimidine synthesis, plays an essential nonredundant role proliferation but complemented homologous CTPS2 isoform outside hemopoietic...
Adoptive transfer of immunoregulatory cells can prevent or ameliorate graft-versus-host disease (GVHD), which remains the main cause nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Mucosal-associated invariant T (MAIT) were recently associated with tissue repair capacities and lower rates GVHD in humans. Here, we analyzed immunosuppressive effect MAIT an vitro model alloreactivity explored their adoptive a preclinical xenogeneic model. We found that cells,...
Abstract De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on CTP synthetases, CTPS1 −2. Partial deficiency in humans has previously been shown to lead immunodeficiency, with impaired expansion T B cells. Here, we examine effects conditional inducible inactivation Ctps1 and/or Ctps2 mouse embryonic development immunity. We report that deletion , but not embryonic-lethal. Tissue cells high proliferation renewal rates, such as...
ABSTRACT The CTP nucleotide is a key precursor of nucleic acids metabolism essential for DNA replication. De novo production relies on synthetases 1 and 2 (CTPS1 2) that catalyze the conversion UTP into CTP. synthetase activity high in proliferating cells including cancer cells, however, respective roles CTPS1 CTPS2 cell proliferation are not known. By inactivation and/or complementation experiments, we showed both differentially required proliferation. was more efficient promoting than...
Abstract Cytidine 5′‐triphosphate synthetase (CTPS) is known to be a central enzyme in the de novo synthesis of CTP. We have recently demonstrated that deficiency CTPS1 associated with an impaired capacity activated lymphocytes proliferate leading combined immunodeficiency disease. In order better document its role immunomodulation, we developed method for measuring CTPS activity human lymphocytes. Using liquid chromatography‐mass spectrometry, quantified by CTP cell lysates. A stable...
Background: The final rate-limiting step in pyrimidine synthesis is the conversion of UTP to CTP which catalyzed by cytidine triphosphate synthase 1 (CTPS1) or CTPS2. A hypomorphic mutation CTPS1 gene has highlighted essential and non-redundant role T B lymphocyte proliferation . These patients exhibit no effects on non-hematopoietic tissues. Thus, selective inhibition represents a novel targeted approach dampen pathological T- B-cell lympho-proliferation. STP938 an orally bioavailable,...
Background: T cell lymphomas are rare haematological cancers characterised by poor response to cytotoxic chemotherapy with resulting unmet clinical need. Recent studies have identified targeted therapies as a promising approach improve outcomes. CTPS1, which catalyses the rate limiting step in pyrimidine synthesis, plays an essential and non-redundant role B proliferation but is complemented homologous CTPS2 isoform outside of haemopoietic system [1]. [1] E. Martin et al., Nature. 2014 Jun...