A5006999109- Pulmonary Hypertension Research and Treatments
- Kruppel-like factors research
- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Congenital heart defects research
- Circular RNAs in diseases
- Plant Molecular Biology Research
- Cardiovascular Issues in Pregnancy
- Neonatal Respiratory Health Research
- Erythrocyte Function and Pathophysiology
- Bone health and treatments
- Adrenal Hormones and Disorders
- Connective Tissue Growth Factor Research
- Glioma Diagnosis and Treatment
- Traumatic Ocular and Foreign Body Injuries
- Macrophage Migration Inhibitory Factor
- Cancer-related molecular mechanisms research
- Cardiac Arrhythmias and Treatments
- Renin-Angiotensin System Studies
- Connective tissue disorders research
- Diet and metabolism studies
- Trauma Management and Diagnosis
- Cardiac pacing and defibrillation studies
- Chemical and Physical Studies
Stanford University
2016-2022
Cardiovascular Institute of the South
2020
Biomedical Research Institute
2020
Stanford Medicine
2018
Willamette University
2017
Temple University Hospital
1999
University of Miami
1964
In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers alleviate disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected carriers (UMCs), FPAH patients, and gender-matched controls to investigate this variation. Our analysis identified features UMC iPSC-ECs related signaling or...
The transition from reversible to irreversible pulmonary arterial hypertension involves vascular senescence and can be countered by senolysis.
Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote beneficial response. We show under LSS, KLF4 interacts with SWI/SNF nucleosome remodeling complex increase accessibility at enhancer sites of homeostatic genes. By combining molecular and computational approaches discover enhancers loop promoters KLF4- LSS-responsive genes stabilize cells...
Rationale: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies.Objectives: cells differentiated from induced pluripotent stem were compared with endothelial same patients idiopathic hypertension, determine whether they shared functional abnormalities altered gene expression patterns...
Background: Bmpr2 (bone morphogenetic protein receptor 2) mutations are critical risk factors for hereditary pulmonary arterial hypertension (PAH) with approximately 20% of carriers developing disease. There is an unmet medical need to understand how environmental factors, such as inflammation, render mutants susceptible PAH. Overexpressing 5-LO (5-lipoxygenase) provokes lung inflammation and transient PAH in +/ - mice. Accordingly, its metabolite, leukotriene B 4 , candidates the second...
Rationale: In pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), p53. Objective: We investigated the vasculoprotective regenerative potential a newly identified PPARγ-p53 factor complex in endothelium. Methods Results: this study, we...
Progressive pseudorheumatoid dysplasia (PPD) is a skeletal characterized by predominant involvement of articular cartilage with progressive joint stiffness. Here we report genetic characterization consanguineous family segregating an uncharacterized from dysplasia. Whole-exome sequencing four affected siblings and their parents identified loss-of-function homozygous mutation in the WISP3 gene, leading to diagnosis PPD individuals. The variant (Chr6: 112382301; WISP3:c.156C>A p.Cys52*)...
Low-velocity firearms represent the majority of civilian gunshot wounds to hand, yet much literature is based on high-velocity injuries. The authors reviewed their treatment regimen for hand and offer a algorithm that emphasizes early debridement fracture stabilization. They also address economic impact society. 121 fractures in 90 patients with treated at an urban trauma center during last 5 years. All were managed irrigation debridement, elevation, intravenous antibiotics, Sixty rigid...
Abstract Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote beneficial response. We show under LSS, KLF4 interacts with SWI/SNF nucleosome remodeling complex increase accessibility at enhancer sites of homeostatic genes. By combining molecular and computational approaches discovered enhancers loop promoters known novel KLF4-...
Transcription factors (TFs) bind DNA sequence motif vocabularies in cis-regulatory elements (CREs) to modulate chromatin state and gene expression during cell transitions. A quantitative understanding of how lexicons influence dynamic regulatory activity has been elusive due the combinatorial nature code. To address this, we undertook multi-omic data profiling dynamics across epidermal differentiation identify 40,103 CREs associated with 3,609 dynamically expressed genes, then applied an...
Introduction: Patients with congenital heart disease (CHD) are at risk of developing progressive pulmonary arterial hypertension (PAH). Timely hemodynamic unloading (HU) by surgical shunt correction usually reverses the arteriopathy, but timepoint when or reason why PAH becomes irreversible remains elusive. Methods: was created in syngeneic rats monocrotalin (MCT) injection and an aorto-caval shunt. For HU different stages, left donor lung transplanted into healthy recipients t14/t21/t28....
Background: Laminar shear stress (LSS) is associated with a vasculoprotective endothelial phenotype, while exposure to disturbed (DSS) linked dysfunction and vascular disease. Epigenetic changes in chromatin accessibility enhancer dynamics are important regulators of gene expression. We hypothesized that LSS DSS induce distinct transcription factors recruit remodelers change the landscape, making it permissive for either protective or disease-related expression profiles. Methods &...