A5005298182- Vascular Malformations Diagnosis and Treatment
- Intracerebral and Subarachnoid Hemorrhage Research
- Intracranial Aneurysms: Treatment and Complications
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Neonatal Respiratory Health Research
- Cardiac pacing and defibrillation studies
- Atrial Fibrillation Management and Outcomes
- SARS-CoV-2 and COVID-19 Research
- Cardiac Arrhythmias and Treatments
- Congenital heart defects research
- Lymphatic System and Diseases
- Kruppel-like factors research
- Pregnancy and preeclampsia studies
- Antiplatelet Therapy and Cardiovascular Diseases
- Forensic Toxicology and Drug Analysis
- Pharmacogenetics and Drug Metabolism
- Hearing, Cochlea, Tinnitus, Genetics
- Moyamoya disease diagnosis and treatment
- Circular RNAs in diseases
- Nuclear Receptors and Signaling
- Eicosanoids and Hypertension Pharmacology
- Platelet Disorders and Treatments
- Cancer Cells and Metastasis
- Congenital Diaphragmatic Hernia Studies
University of Pennsylvania
2016-2025
Cardiovascular Institute of the South
2019-2025
Cardiovascular Institute Hospital
2021
Translational Therapeutics (United States)
2018
University of Auckland
2017
Inserm
2014
Children's Hospital of Philadelphia
2014
Sorbonne Paris Cité
2014
Université Paris Cité
2014
Assistance Publique – Hôpitaux de Paris
2014
Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial (HECs) within the developing embryo. Understanding origin ontogeny HSPCs is considerable interest potential therapeutic value. It has been proposed that murine placenta contains HECs differentiate into HSPCs. However, during human gestation in aorta considerably earlier than when they can first be detected placenta, suggesting may primarily serve as niche. We found Runx1...
Structural remodeling of human atria plays a key role in sustaining atrial fibrillation (AF), but insufficient quantitative analysis structure impedes the treatment AF. We aimed to develop novel 3-dimensional (3D) structural and computational simulation tool that could reveal contributors reentrant AF drivers.High-resolution panoramic epicardial optical mapping coronary-perfused explanted intact (63-year-old woman, chronic hypertension, heart weight 608 g) was conducted during sinus rhythm...
Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset earlier and more severe individuals with mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation lipopolysaccharide derived the gut microbiome. These findings suggest gut-brain disease axis but fail to define it explain...
In recent decades, treatments for myocardial infarction (MI), such as stem and progenitor cell therapy, have attracted considerable scientific clinical attention but failed to improve patient outcomes. These efforts indicate that more rigorous mechanistic functional testing of potential MI therapies is required. Recent studies suggested augmenting post-MI lymphatic growth via VEGF-C administration improves cardiac function. However, the mechanisms underlying this proposed therapeutic...
The purpose of this study was to determine important genes, functions, and networks contributing the pathobiology cerebral cavernous malformation (CCM) from transcriptomic analyses across 3 species 2 disease genotypes. Sequencing RNA laser microdissected neurovascular units 5 human surgically resected CCM lesions, mouse brain microvascular endothelial cells, Caenorhabditis elegans with induced Ccm gene loss, their respective controls provided differentially expressed genes (DEGs). DEGs C....
Cerebral cavernous malformations (CCMs) are dilated capillaries causing epilepsy and stroke. Inheritance of a heterozygous mutation in CCM3/PDCD10 is responsible for the most aggressive familial form disease. Here we studied differences commonalities between transcriptomes microdissected lesional neurovascular units (NVUs) from acute chronic vivo Ccm3/Pdcd10ECKO mice, cultured brain microvascular endothelial cells (BMECs) Ccm3/Pdcd10ECKO.We identified 2409 differentially expressed genes...
Cerebral cavernous malformations (CCMs) form following loss of the CCM protein complex in brain endothelial cells due to increased MEKK3 signaling and KLF2/4 transcription factor expression, but downstream events that drive lesion formation remain undefined. Recent studies have revealed lesions expand by incorporating neighboring wild-type cells, indicative a cell nonautonomous mechanism. Here we find ADAMTS5 reduced neonatal mouse model. Conversely, gain conferred early genesis absence...
The GPR124/RECK/WNT7 pathway is an essential regulator of CNS angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endothelial adhesion seven-pass transmembrane protein, associates with RECK, which binds stabilizes newly synthesized WNT7 that transferred to frizzled (FZD) initiate canonical β-catenin signaling. GPR124 remains enigmatic: although its extracellular domain (ECD) essential, the poorly conserved intracellular (ICD) appears be variably required in mammals versus...
Abstract Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, pilot study had suggested potential microbiome differences between non-CA individuals based 16S rRNA gene sequencing. We here assess a larger cohort human subjects with without CA, among different clinical features, conduct more definitive microbial analyses using...
Angiotensin-converting enzyme 2 (ACE2) is the cell-surface receptor for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). While its central role in Disease 2019 (COVID-19) pathogenesis indisputable, there remains significant debate regarding of this transmembrane carboxypeptidase disease course. These include soluble versus membrane-bound ACE2, as well ACE2-independent mechanisms that may contribute to viral spread. Testing these roles requires vivo models. Here, we report...
Nurr1, an NGFI-B nuclear orphan receptor, which transactivates promoters through response element (NBRE), is strongly induced by parathyroid hormone the cAMP-protein kinase A signaling pathway in osteoblasts. Here, we demonstrate that multiple agents activating diverse pathways osteoblasts induce Nurr1. The strongest Nurr1 inducers were activators of A-coupled signaling, followed protein C- and calcium-coupled activators. Receptor tyrosine had minimal effect, whereas serine/threonine no...
Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA proteins, were expressed in prostate carcinoma (PC‐3, DU‐145 LNCaP) cells. 11,12‐Epoxyeicosatrienoic acid (11,12‐EET) was the major arachidonic metabolite these Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N‐methylsulfonyl‐6‐(2‐propargyloxyphenyl)hexanamide [MS‐PPOH]) inhibited tonic (basal) invasion migration (motility) while exogenously added induced cell motility concentration‐dependent manner. An epidermal...
The cannabinoid receptor type 1 (CB1) is a G protein-coupled that activated in an autocrine fashion by the endocannabinoids (EC), N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). CB1 its endogenous synthetic agonists are emerging as therapeutic targets several cancers due to their ability suppress carcinoma cell invasion migration. However, mechanisms regulates motility not well understood. In this study, we examined molecular diminish migration upon activation prostate...
The Heart of Glass (HEG) receptor binds KRIT1 and functions with KRIT1, CCM2, PDCD10 in a common signaling pathway required for heart vascular development. Mutations also underlie human cerebral cavernous malformation (CCM) postnatal loss these genes the mouse endothelium results rapid CCM formation. Here, we test role HEG formation mice humans.We constitutively or conditionally deleted Heg Ccm2 genetically modified mice. Mouse embryos, brain, retina tissues were analyzed to assess lesion...