A5053338938- Pulmonary Hypertension Research and Treatments
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- MicroRNA in disease regulation
- Neonatal Respiratory Health Research
- Wnt/β-catenin signaling in development and cancer
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Axon Guidance and Neuronal Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Nitric Oxide and Endothelin Effects
- Ecology and Vegetation Dynamics Studies
- Nuclear Receptors and Signaling
- Rangeland and Wildlife Management
- Congenital Heart Disease Studies
- Cardiomyopathy and Myosin Studies
- PI3K/AKT/mTOR signaling in cancer
- Congenital heart defects research
- Adenosine and Purinergic Signaling
- Wildlife Ecology and Conservation
- Lung Cancer Treatments and Mutations
- Cardiovascular Effects of Exercise
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
Université Laval
2020-2023
Stanford University
2012-2022
Institut Universitaire de Cardiologie et de Pneumologie de Québec
2019-2022
Canadian Heart Research Centre
2021
Cardiovascular Institute of the South
2014-2019
Stanford Medicine
2013-2018
Mie University
2012
Buck Institute for Research on Aging
2009-2011
Dominican University of California
2010-2011
Pulmonary arterial hypertension (PAH) is a life-threatening disorder of the pulmonary circulation associated with loss and impaired regeneration microvessels. Reduced pericyte coverage microvessels pathological feature PAH caused partly by inability pericytes to respond signaling cues from neighboring microvascular endothelial cells (PMVECs). We have shown that activation Wnt/planar cell polarity pathway required for recruitment, but whether production release specific Wnt ligands PMVECs are...
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disorder characterized by progressive loss of microvessels. Although mutations in the bone morphogenetic receptor 2 (BMPR2) are found 80% heritable and ∼15% patients with IPAH, their low penetrance (∼20%) suggests that other unidentified genetic modifiers required for manifestation disease phenotype. Use whole-exome sequencing (WES) has recently led to discovery novel susceptibility genes PAH, but whether WES can also...
The authors show that increased poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) and pyruvate kinase muscle isozyme 2 (PKM2) expression is a common feature of decompensated right ventricle in patients with pulmonary arterial hypertension animal models. find vitro overactivated PARP1 promotes cardiomyocyte dysfunction by favoring PKM2 nuclear function, glycolytic gene expression, activation factor κB-dependent proinflammatory factors. Pharmacologic genetic inhibition or enforced...
Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary smooth muscle cells (PASMCs) growth, partially in response to PDGF-BB but whether this dependent on β-catenin (βC) activation unclear. Compared healthy cells, PAH PASMCs demonstrate higher levels of proliferation both at baseline and with that correlate GSK3β βC activation. We show knockdown not Wnt5a stimulation reduces growth normalizes proliferation. These findings support cross-talk between PDGF Wnt signaling...
Pulmonary arterial hypertension (PAH) is a debilitating disease associated with progressive vascular remodeling of distal pulmonary arteries leading to elevation artery pressure, right ventricular hypertrophy, and death. Although presenting high levels DNA damage that normally jeopardize their viability, smooth muscle cells (PASMCs) from patients PAH exhibit cancer-like proproliferative apoptosis-resistant phenotype accounting for lumen obliteration. In cancer cells, overexpression the...
In this digital era, there is a growing tendency to use the popular Internet site YouTube as new electronic-learning (e-learning) means for continuing medical education. Heart transplantation (HTx) remains most viable option patients with end-stage heart failure or severe coronary artery disease. There are plenty of freely accessible videos providing information about HTx.The aim present study determine effectiveness an e-learning source on HTx.In order carry out study, was searched uploaded...
Endothelial cell (EC) dysfunction plays a role in the pathobiology of occlusive vasculopathy pulmonary arterial hypertension (PAH). Purinergic signaling pathways, which consist extracellular nucleotide and nucleoside-mediated through specific receptors, are known to be important regulators vascular tone remodeling. Therefore, we hypothesized that abnormalities purinergic microenvironment associated with PAH. Enzymatic clearance is crucial terminate unnecessary activation; one most abundantly...
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH), but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) involved in metabolism METH other amphetamine-like compounds, we postulated loss function variants could contribute to METH-PAH. Although no difference CYP2D6 expression was seen by lung immunofluorescence, CES1 significantly reduced endothelium METH-PAH microvessels. Mass spectrometry analysis...
Reduced endothelial-pericyte interactions are linked to progressive small vessel loss in pulmonary arterial hypertension (PAH), but the molecular mechanisms underlying this disease remain poorly understood. To identify relevant gene candidates associated with aberrant pericyte behavior, we performed a transcriptome analysis of patient-derived donor control and PAH lung pericytes followed by functional genomics analysis. Compared cells, had significant enrichment genes involved various...
Angioplasty and stenting is the primary treatment for flow-limiting atherosclerosis; however, this strategy limited by pathological vascular remodeling. Using a systems approach, we identified role network hub gene glutathione peroxidase-1 (GPX1) in remodeling following human blood vessel stenting. Constitutive deletion of Gpx1 atherosclerotic mice recapitulated phenotype increased smooth muscle cell (VSMC) proliferation plaque formation. In an independent patient cohort, variant pair...
Rationale: Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by abnormally elevated pulmonary pressures and right ventricular failure. Excessive proliferation resistance to apoptosis of artery smooth muscle cells (PASMCs) one the most important drivers vascular remodeling in PAH, for which available treatments have limited effectiveness.Objectives: To gain insights into mechanisms leading development disease identify new actionable targets.Methods: Protein...
Introduction: Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH incompletely understood. We hypothesised that activation microvascular endothelial cells (PMVECs) required for angiogenesis, and its contributes to PAH. Methods: Lung tissue PMVECs from healthy patients were screened production. Global endothelial-specific Wnt7a −/– mice generated exposed chronic hypoxia Sugen-hypoxia (SuHx)....
Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but APP-dependent network involved has not been defined. Here, we report a novel consensus sequence for interaction with PDZ-1 and PDZ-2 domains APP-interacting proteins Mint1, Mint2, Mint3 (X11α, X11β, X11γ), multiple interactors these proteins, finding that transcriptional coactivators are highly represented among interactors. Furthermore, show set leads to nuclear...
Drug-induced pulmonary arterial hypertension (D-PAH) is a form of World Health Organization Group 1 (PH) defined by severe small vessel loss and obstructive vasculopathy, which leads to progressive right heart failure death. To date, 16 different compounds have been associated with D-PAH, including anorexigens, recreational stimulants, more recently, several Food Drug Administration-approved medications. Although the clinical manifestation, pathology, hemodynamic profile D-PAH are...
Rationale: Pulmonary hypertension (PH) is characterized by progressive elevation in pulmonary pressure and loss of small arteries. As bone morphogenetic proteins promote angiogenesis recruiting the Wnt/β-catenin pathway, we proposed that β-catenin activation could reduce induce regeneration arteries (PAs) attenuate PH. Objective: This study aims to establish role protecting endothelium stimulating compensatory after injury. Methods Results: To assess impact on chronic hypoxia-induced PH,...
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation resistance to apoptosis (as seen in cancer cells) PA smooth muscle cells (PASMCs) major pathological hallmark contributing vascular remodeling PAH, for which current therapies have only limited effects. Emerging evidence points toward critical role Enhancer Zeste Homolog 2 (EZH2) cell...
The amyloid-β protein precursor (AβPP) has been implicated in Alzheimer's disease (AD) not only as a of the peptide but also mediator signal transduction. We recently identified novel mediators AβPP signaling via intera
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by exuberant tissue remodelling and associated with high unmet medical needs. Outcomes are even worse when IPF results in secondary hypertension (PH). Importantly, exaggerated resistance to cell death, excessive proliferation enhanced synthetic capacity key endophenotypes of both fibroblasts artery smooth muscle cells, suggesting shared molecular pathways. Under persistent injury, sustained activation the DNA damage...
Trifluoperazine (TFP), an antipsychotic drug approved by the Food and Drug Administration, has been show to exhibit anti-cancer effects. Pulmonary arterial hypertension (PAH) is a devastating disease characterized progressive obliteration of small pulmonary arteries (PAs) due exaggerated proliferation resistance apoptosis PA smooth muscle cells (PASMCs). However, therapeutic potential TFP for correcting cancer-like phenotype PAH-PASMCs improving PAH in animal models remains unknown. PASMCs...
Angiogenesis is the process by which new blood vessels are formed from existing vessels. New vessel growth requires coordinated endothelial cell proliferation, migration, and alignment to form tubular structures followed recruitment of pericytes provide mural support facilitate maturation. Current in vitro culture approaches cannot fully reproduce complex biological environment where cells interact produce functional We present a novel application vivo matrix gel plug assay study...
Non-native plant invasions can lead to staggering ecological and economic costs. Thus, land managers are concerned about vectors of seed propagule introduction onto public lands. Because horses one several potential non-native dispersal, we summarize interpret existing literature identify impacts horse use on spread in natural areas. Several studies indicate seeds germinate after digestion by horses. In addition their ability carry viable feces, the indicates trample native vegetation, cause...