A5083017074- Vascular Malformations and Hemangiomas
- Oral and gingival health research
- Vascular Malformations Diagnosis and Treatment
- Vasculitis and related conditions
- Hedgehog Signaling Pathway Studies
- Renal Diseases and Glomerulopathies
- Electrolyte and hormonal disorders
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Autoimmune Bullous Skin Diseases
- Dialysis and Renal Disease Management
- Systemic Lupus Erythematosus Research
- Birth, Development, and Health
- Tumors and Oncological Cases
- Genetic Syndromes and Imprinting
- Ear and Head Tumors
- Islanding Detection in Power Systems
- Pancreatic function and diabetes
- Neurofibromatosis and Schwannoma Cases
- Intracranial Aneurysms: Treatment and Complications
Inserm
2019-2024
Université Paris Cité
2021-2024
Institut Necker Enfants Malades
2018-2024
Université Sorbonne Nouvelle
2023
Assistance Publique – Hôpitaux de Paris
2022-2023
Hôpital Necker-Enfants Malades
2022-2023
Alplesib exerts therapeutic effects in a mouse model of lymphatic anomalies and six patients with malformations over 6 months’ treatment.
PIK3CA-related overgrowth spectrum (PROS) includes rare genetic conditions due to gain-of-function mutations in the PIK3CA gene. There is no approved medical therapy for patients with PROS, and alpelisib, an inhibitor oncology, showed promising results preclinical models patients. Here, we report first time outcome of two infants PROS having life-threatening treated alpelisib (25 mg) monitored pharmacokinetics. Patient 1 was 8-mo-old girl voluminous vascular malformation. 2 a 9-mo-old boy...
gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such
Proliferative glomerulonephritis is a severe condition often leading to kidney failure. There significant lack of effective treatment for these disorders. Here, following the identification somatic PIK3CA gain-of-function mutation in podocytes patient, we demonstrate using multiple genetically engineered mouse models, single-cell RNA sequencing and spatial transcriptomics crucial role played by this pathway proliferative development promoting podocyte proliferation, dedifferentiation...
PIK3CA-related overgrowth syndrome (PROS) is a genetic disorder caused by somatic mosaic gain-of-function mutations of PIK3CA. Clinical presentation patients diverse and associated with endocrine disruption. Adipose tissue frequently involved, but its role in disease development progression has not been elucidated. Here, we created mouse model adipose that recapitulates patient phenotype. We demonstrate PIK3CA mutation leads to GLUT4 membrane accumulation negative feedback loop on insulin...
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK, an endothelial transmembrane receptor signaling through PIK3CA. Venous associated with pain, bleedings, thrombosis, pulmonary embolism, esthetic deformities and, in severe cases, life-threatening situations. No authorized medical treatment exists for patients malformations. Here, we created a mouse model PIK3CA-related capillary that replicates patient phenotypes. We...
Hemifacial myohyperplasia (HFMH) is a rare cause of facial asymmetry exclusively involving muscles. The underlying and the mechanism disease progression are unknown. Here, we identified somatic gain-of-function mutation PIK3CA in five pediatric patients with HFMH. To understand physiopathology muscle hypertrophy this context, created mouse model carrying specifically skeletal led to striated cell hypertrophy, mitochondria dysfunction, hypoglycemia low circulating insulin levels. Alpelisib...
CKD is associated with the loss of functional nephr ons, leading to increased mechanical and metabolic stress in remaining cells, particularly for cells constituting filtration barrier, such as podocytes. The failure podocytes mount an adequate response can lead further nephron disease progression. However, mechanisms that regulate this degenerative process kidney are unknown.We combined vitro, vivo, organ-on-chip approaches identify RE1-silencing transcription factor (REST), a repressor...