A5007636677- Atherosclerosis and Cardiovascular Diseases
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Cancer-related molecular mechanisms research
- Adipokines, Inflammation, and Metabolic Diseases
- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Apelin-related biomedical research
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and disorders
- RNA modifications and cancer
- HIV-related health complications and treatments
- Genetic Mapping and Diversity in Plants and Animals
- Cellular Mechanics and Interactions
- Angiogenesis and VEGF in Cancer
- Cell Image Analysis Techniques
- Heat shock proteins research
- Genetic Syndromes and Imprinting
- Hormonal Regulation and Hypertension
- Ferroptosis and cancer prognosis
- Congenital heart defects research
- Diet, Metabolism, and Disease
- Nuclear Receptors and Signaling
Vanderbilt University Medical Center
2023-2025
University of Arizona
2017-2024
Vanderbilt University
2023-2024
University of California, Irvine
2023-2024
University of California, Los Angeles
2023
Environmental Education Exchange
2023
Lindsey Wilson College
2017
[Figure: see text].
Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities functional states remain poorly understood. Here, we report a genome-wide assessment regulatory landscapes primary human aortic endothelial (HAECs) under basal activated conditions, enabling inference transcription factor networks that direct homeostatic pro-inflammatory programs. We demonstrate 43% detected enhancers EC-specific contain SNPs...
Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation vascular endothelium contributing atherosclerosis, the cause coronary artery disease (CAD) ischemic stroke (IS). Conversely, unidirectional promotes quiescent...
While the immediate and transitory response of breast cancer cells to pathological stiffness in their native microenvironment has been well explored, it remains unclear how stiffness-induced phenotypes are maintained over time after cell dissemination vivo. Here, we show that fibrotic-like matrix promotes distinct metastatic cells, which preserved transition softer microenvironments, such as bone marrow. Using differential gene expression analysis stiffness-responsive establish a multigenic...
Functional consequences of genetic variation in the noncoding human genome are difficult to ascertain despite demonstrated associations common, complex disease traits. To elucidate properties functional SNPs with effects endothelial cells (ECs), we utilized our previous molecular quantitative trait locus (molQTL) analysis for transcription factor binding, chromatin accessibility, and H3K27 acetylation nominate a set likely SNPs. Together information from genome-wide association studies...
Abstract Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in feasibility reproducibility CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to 14,145 individuals across four international cohorts with diverse ascertainment methods establish, validate characterize a score. In cohort around 22,000 UK Biobank, score was associated reduced risk all-cause...
Introduction: The prevalence of hepatic steatosis—a central and early phenotype in multi-system metabolic dysfunction—is increasing parallel with the obesity pandemic, calling for novel approaches prevention treatment. Hypothesis: We hypothesized that circulating proteome may reflect cell specific mechanisms steatosis. Methods: Using multi-modality imaging broad proteomics approximately 5,000 individuals across 3 diverse cohorts (CARDIA, Cameron County Hispanic Cohort, UK Biobank), we...
Regulation of gene expression requires the combinatorial binding sequence-specific transcription factors (TFs) at promoters and enhancers. Prior studies showed that alterations in spacing between TF sites can influence promoter enhancer activity. However, relative importance resulting from naturally occurring insertions deletions (InDels) has not been systematically analyzed. To address this question, we first characterized genome-wide relationships 73 TFs human K562 cells as determined by...
CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which associated with genetic risk coronary artery disease. In this study, we functionally characterized noncoding regulatory elements carrying disease that risks single-nucleotide polymorphisms and studied their role in regulation
Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated dynamics of transcription chromatin in response dual integrating nascent RNA imaging mass spectrometry, sequencing, amplification-independent mRNA quantification, assay for transposase-accessible using sequencing (ATAC-seq), factor profiling. Costimulation with interferon-gamma (IFNγ) tumor...
ABSTRACT Coronary artery disease (CAD) is one of the major causes mortality worldwide. Recent genome-wide association studies have started to unravel genetic architecture disease. Such efforts identified Calcitonin receptor-like (CALCRL), an important mediator endothelial fluid shear stress response, associated with CAD risk variants. In this study we functionally characterized non-coding regulatory elements carrying risks SNPs and studied their role in regulation CALCRL expression cells. We...
Endothelial cells (ECs), macrophages, and vascular smooth muscle (VSMCs) are major cell types in atherosclerosis progression, heterogeneity EC sub-phenotypes becoming increasingly appreciated. Still, studies quantifying across whole transcriptomes epigenomes both vitro vivo models lacking.To create an dataset to study human heterogeneity, multiomic profiling concurrently measuring accessible chromatin the same single was performed on six distinct primary cultures of aortic ECs (HAECs). To...
Chronic systemic inflammation contributes to a substantially elevated risk of myocardial infarction in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the vasoconstriction, inflammation, and thrombosis that contribute cardiovascular disease. Our objective was study effects plasma from PLWH on endothelial (EC) function, hypothesis cytokines chemokines are major drivers EC activation. We first broadly phenotyped chemokine...
Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes both vitro vivo models are lacking. Multiomic profiling concurrently measuring accessible chromatin the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic atherosclerotic microenvironment vitro....
Abstract Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed characterize endothelial (EC) chemokines, cytokine, chemokine receptors PLWH, hypothesizing that our cohort, glucose intolerance contributes their differential expression implicated...