A5007973133- Atherosclerosis and Cardiovascular Diseases
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Nuclear Structure and Function
- Nuclear Receptors and Signaling
- Hormonal Regulation and Hypertension
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Galectins and Cancer Biology
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- T-cell and B-cell Immunology
- Cardiovascular Function and Risk Factors
- Protein Degradation and Inhibitors
- Cytomegalovirus and herpesvirus research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- FOXO transcription factor regulation
- Circular RNAs in diseases
- Adrenal and Paraganglionic Tumors
- Telomeres, Telomerase, and Senescence
- Viral Infections and Immunology Research
- GDF15 and Related Biomarkers
- Genetic factors in colorectal cancer
University of Virginia
2021-2025
Office of Public Health Genomics
2022-2023
The University of Texas Health Science Center at Houston
2020-2022
Brown Foundation
2020
Baylor College of Medicine
2018
Inserm
2016-2018
Université Paris-Saclay
2016-2018
Université Paris-Sud
2016-2018
Instituto Politécnico Nacional
2018
Rationale: Mutations in the LMNA gene, encoding nuclear inner membrane protein lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are common causes of death Objective: The objective this study was identify therapeutically target responsible mechanism(s) for cardiac phenotype Methods Results: Whole-heart RNA sequencing performed before onset dysfunction Lmna −/− matched control mice. Differentially expressed...
Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is major cause death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, sudden death. There no specific therapy for LMNA-associated cardiomyopathy. We report that deletion Lmna cardiomyocytes mice leads to severe cardiac dysfunction, conduction defect, ventricular fibrosis, apoptosis, premature within 4 weeks. The phenotype similar cardiomyopathy...
Introduction: Mutations in the LMNA gene, encoding Lamin A/C (LMNA), are established causes of dilated cardiomyopathy (DCM). The phenotype is typically characterized by progressive cardiac conduction defects, arrhythmias, heart failure, and premature death. DCM primarily considered a disease myocytes. However, also expressed other cell types, including fibroblasts. Aim: purpose study was to determine contribution fibroblasts caused deficiency. Methods Results: Lmna gene deleted crossing...
Herpes simplex virus-1 (HSV-1) establishes a lifelong latent infection in neurons and reactivation from this state is the cause of recurrent oral ocular infections, herpes keratitis, encephalitis. Neuronal conditions during initial HSV-1 have long-term impact on latency, modulating how responsive genomes are to and, therefore, their ability disease. Type I interferon (IFNα) exposure results promyelocytic leukemia nuclear-body (PML-NB) formation more restrictive form latency. Here we...
Summary Vascular smooth muscle cells (SMCs) normally exist in a contractile state but can undergo fate switching to produce various cell phenotypes response pathologic stimuli 1–3 . In atherosclerosis, these phenotypically modulated SMCs regulate plaque composition and influence the risk of major adverse cardiovascular events 4,5 We found that PRDM16, transcription factor is genetically associated with disease, highly expressed arterial downregulated during SMC human mouse atherosclerosis....
Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While number scRNA-seq datasets available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies allow rapid exploration re-analysis single-cell datasets, particularly in cardiovascular field. We previously introduced PlaqView, an open-source web portal for published atherosclerosis datasets. Now, we...
Background Mutations in the
The MR (mineralocorticoid receptor) antagonists belong to the current therapeutic armamentarium for management of cardiovascular diseases, but mechanisms conferring their beneficial effects are poorly understood. Part is because regulation L-type Cav1.2 Ca2+ channel expression, which generated by tissue-specific alternative promoters as a long cardiac or short vascular N-terminal transcripts.To analyze molecular aldosterone, through MR, modulates expression and function in manner.In primary...
Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach WGS 4949 cases and 17,494 controls European ancestry from NHLBI TOPMed program. We estimate CAD at 34.3% assuming a prevalence 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) with low linkage disequilibrium (LD) score ~50% heritability. also investigate enrichment using diverse set...
Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms these during atherosclerosis remain unclear. We incorporated local ancestry haplotypes to identify quantitative trait expression (eQTLs) splicing (sQTLs) arteries from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported...
Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms these during atherosclerosis remain unclear. We incorporated local ancestry haplotype information to identify quantitative trait (QTL) gene expression splicing arteries obtained from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were...
Abstract Coronary artery disease (CAD) is a complex inflammatory involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis -regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells coronary segments from 41 patients varying stages which revealed 14 distinct cellular clusters. We mapped...
Abstract Coronary artery disease (CAD) and atherosclerosis are characterized by plaque formation in the arteries wall. CAD progression involves complex interactions phenotypic plasticity within between distinct vascular immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but reported phenotypes humans remain controversial. Here, we meta-analyzed four scRNA-seq datasets, creating first map of human diversity...
Coronary artery disease (CAD) and atherosclerosis are characterized by plaque formation in the arteries wall. CAD progression involves complex interactions phenotypic plasticity within between distinct vascular immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but reported phenotypes humans remain controversial. Here, we meta-analyzed four scRNA-seq datasets, creating first map of human diversity atherosclerosis. We...
Introduction: Atherosclerosis is a chronic inflammatory process driven by plaque formation in the major elastic arteries leading to reduced blood flow, coronary artery disease (CAD), myocardial infarction and stroke. Several single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures CAD-relevant tissues; however, there remains variability on reported cell phenotypes humans. We evaluated overall hypothesis that distinct smooth muscle (SMC)...