A5025369486- Congenital heart defects research
- Pulmonary Hypertension Research and Treatments
- Congenital Heart Disease Studies
- Cardiovascular Function and Risk Factors
- Tissue Engineering and Regenerative Medicine
- Antifungal resistance and susceptibility
- Pluripotent Stem Cells Research
- Genetics, Aging, and Longevity in Model Organisms
- Cardiovascular Effects of Exercise
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Respiratory Support and Mechanisms
- Photoreceptor and optogenetics research
- Hemodynamic Monitoring and Therapy
- Neuroscience and Neural Engineering
- Gut microbiota and health
- Cardiac Valve Diseases and Treatments
- Mitochondrial Function and Pathology
- Cardiac Structural Anomalies and Repair
- Cardiac Fibrosis and Remodeling
- Anesthesia and Neurotoxicity Research
- Cancer-related gene regulation
- Sepsis Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Johns Hopkins University
2014-2024
Johns Hopkins Medicine
2015-2024
Northwestern University
2018
University of Washington
2018
Medical University of South Carolina
2018
Johns Hopkins Hospital
2015-2016
Massachusetts General Hospital
2008-2010
Harvard University
2008-2010
Right ventricular (RV) functional reserve affects capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated systemic sclerosis (SSc-PAH) has a substantially worse than idiopathic (IPAH), even though many measures of resting RV function vascular load are similar. We therefore tested the hypothesis that is depressed SSc-PAH patients.RV pressure-volume relations were prospectively measured IPAH (n=9) (n=15) at rest during incremental atrial pacing or supine...
Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, their mammalian orthologues, scavenger SCARF1 CD36, mediate host defense against two prototypic pathogens, Cryptococcus neoformans Candida albicans. C03F11.1 mediated antimicrobial peptide production were necessary for nematode survival after C. infection. CD36 cytokine required macrophage binding neoformans, control of infection...
Candida albicans colonizes the human gastrointestinal tract and can cause life-threatening systemic infection in susceptible hosts. We study here C. virulence determinants using nematode Caenorhabditis elegans a pathogenesis system that models candidiasis. The yeast form of is ingested into digestive tract. In liquid media, cells then undergo morphological change to hyphae, which results aggressive tissue destruction death nematode. Several lines evidence demonstrate hyphal formation...
Prokaryote-eukaryote interactions are ubiquitous and have important medical environmental significance. Despite this, a paucity of data exists on the mechanisms pathogenic consequences bacterial-fungal encounters within living host. We used nematode Caenorhabditis elegans as substitute host to study between two ecologically related clinically troublesome pathogens, prokaryote, Acinetobacter baumannii, eukaryote, Candida albicans. After co-infecting C. with these organisms, we observed that...
The discovery of the first heart field (FHF) and second (SHF) led us to understand how cardiac lineages structures arise during development. However, it remains unknown they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under control FHF/SHF markers, respectively. GFP+ RFP+ appear from two distinct areas develop in a complementary fashion. Transcriptome analysis shows high degree similarities embryonic cells. Bmp Wnt...
Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared isolated postcapillary. However, it remains unclear whether increased mortality in is simply result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) measure afterload, reflecting both resistive pulsatile components. We aimed test Ea discriminates survivors from nonsurvivors patients if does so better than other hemodynamic...
Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived exhibit fetal-like characteristics remain immature in a dish. This has emerged as major obstacle their application late-onset diseases. We previously showed that there is neonatal arrest of long-term cultured cardiomyocytes (PSC-CMs). Here, we demonstrate PSC-CMs mature into adult CMs when transplanted hearts. became similar to morphology, structure, function...
Abstract Heart failure is a major public health problem affecting over 23 million people worldwide. In this study, we present the results of large scale meta-analysis heart GWAS and replication in comparable sized cohort to identify one known two novel loci associated with failure. sub-phenotyping shows that new locus chromosome 1 left ventricular adverse remodeling clinical failure, response different initial cardiac muscle insults. Functional characterization fine-mapping reveal putative...
Abstract Cardiomyocytes undergo significant structural and functional changes after birth, these fundamental processes are essential for the heart to pump blood growing body. However, due challenges of isolating single postnatal/adult myocytes, how individual newborn cardiomyocytes acquire multiple aspects mature phenotype remains poorly understood. Here we implement large-particle sorting analyze myocytes from neonatal adult hearts. Early exhibit wide-ranging transcriptomic size...
Candida albicans is an opportunistic human fungal pathogen that normally resides in the gastrointestinal tract and on skin as a commensal but can cause life-threatening invasive disease. Salmonella enterica serovar Typhimurium gram-negative bacterial causes significant amount of infection humans. Both these organisms are also pathogenic to nematode Caenorhabditis elegans, causing persistent gut leading worm death. In present study, we used previously developed C. elegans polymicrobial model...
Embryos devoid of autonomic innervation suffer sudden cardiac death. However, whether neurons have a role in heart development is poorly understood. To investigate if sympathetic impact cardiomyocyte maturation, we co-cultured phenotypically immature cardiomyocytes derived from human induced pluripotent stem cells with mouse ganglion neurons. We found that 1) multiple structure and ion channel genes related to maturation were up-regulated when neurons; 2) sarcomere organization connexin-43...
Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, extent to which functions influenced by satellite vivo remains unclear. Here, we show that critical for metabolism, survival, and activity of neurons modulate autonomic behaviors mice. Adult ablation results impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, loss neurons. However, persisting have elevated activity, glia-ablated mice increased...
Neuropeptide Y (NPY) is best known for its effects in the brain as an orexigenic and anxiolytic agent reducing energy expenditure. NPY also co-expressed with norepinephrine (NE) sympathetic neurons. Although generally considered to modulate noradrenergic responses, specific roles autonomic physiology remain under-appreciated. Here, we show that sympathetic-derived essential metabolic cardiovascular regulation mice. NE are 90% of prevertebral neurons only 43% paravertebral NPY-expressing...
Background The effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time right ventricular (RV) load is unknown. Methods To determine the association HR BSA with measures RV load, we studied three large patient cohorts including subjects 1) known or suspected arterial hypertension (PAH) (n = 1008), 2) due to left disease 468), 3) end-stage failure reduced ejection fraction 150). corroborate these associations an individual level, performed additional analysis using...
Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response may initially be protective, but when prolonged, have been implicated in atherogenesis diabetic conditions. Triglycerides free fatty acids (FFAs) are elevated patients with diabetes contribute to ER stress. We sought evaluate effect of acute FFA elevation on endothelial circulating white cells.
Neurons regulate cardiomyocyte proliferation through clock genes.
The heart develops in a synchronized sequence of proliferation and differentiation cardiac progenitor cells (CPCs) from two anatomically distinct pools cells, the first field (FHF) second (SHF). Congenital defects arise upon dysregulation these processes, many which are restricted to derivatives FHF or SHF. Of conserved set signaling pathways that regulate development, Wnt pathway has long been known for its importance SHF development. source such Wnts remained elusive, though it postulated...
Pulmonary vascular dysfunction is associated with adverse prognosis in patients the acute respiratory distress syndrome; however, prognostic impact of pulmonary arterial compliance syndrome not established.We performed a retrospective analysis 363 subjects who had complete baseline right heart catheterization data from Fluid and Catheter Treatment Trial to test whether at over course treatment predicted mortality.Baseline (hazard ratio, 1.18 per interquartile range 1/pulmonary compliance;...