A5003077515- Atherosclerosis and Cardiovascular Diseases
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Nuclear Receptors and Signaling
- Phosphodiesterase function and regulation
- Immune cells in cancer
- Galectins and Cancer Biology
- Wound Healing and Treatments
- Bioinformatics and Genomic Networks
- Phagocytosis and Immune Regulation
- Congenital heart defects research
- Sleep and related disorders
- Circular RNAs in diseases
- Genetic factors in colorectal cancer
- Protein Tyrosine Phosphatases
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Cardiovascular Disease and Adiposity
- Lipoproteins and Cardiovascular Health
- Genetic Mapping and Diversity in Plants and Animals
University of Virginia
2012-2025
Office of Public Health Genomics
2018-2025
Southwest Regional Wound Care Center
2020-2025
Deakin University
2023-2024
Stanford University
2012-2023
Palo Alto University
2019
Charlottesville Medical Research
2018
Cardiovascular Institute of the South
2013-2018
Stanford Medicine
2014-2017
University of Rochester
2007-2016
Significance Here, we present unequivocal evidence of physical association AMPK holoenzymes with mitochondrial reticulum (mitoAMPK) across multiple mouse tissues conservation in human skeletal muscle and heart. We demonstrate that mitoAMPK is activated heterogeneously the by energetic stress. Finally, suggests activation required for mitophagy. propose responds to microenvironment cues maintain homeostasis through quality control.
Cyclic nucleotide phosphodiesterases (PDEs) through the degradation of cGMP play critical roles in maintaining cardiomyocyte homeostasis. Ca(2+)/calmodulin (CaM)-activated cGMP-hydrolyzing PDE1 family may a pivotal role balancing intracellular Ca(2+)/CaM and signaling; however, its function cardiomyocytes is unknown.Herein, we investigate Ca(2+)/CaM-stimulated regulating pathological hypertrophy neonatal adult rat ventricular myocytes heart vivo.Inhibition activity using PDE1-selective...
Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded this contribute to disease. We have previously demonstrated that loss of one candidate gene locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice vascular SMC apoptosis and aneurysm progression. Here, we investigated role Cdnk2b atherogenesis found a mouse model atherosclerosis, deletion promoted advanced development atherosclerotic plaques...
Abstract Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic environmental risk factors. Meta-analyses genome-wide association studies have identified >150 loci associated with CAD myocardial infarction susceptibility in humans. A majority these variants reside non-coding regions are co-inherited hundreds candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic...
Abstract Summary Identification of functional transcription factors that regulate a given gene set is an important problem in regulation studies. Conventional approaches for identifying factors, such as DNA sequence motif analysis, are unable to predict binding specific and not sensitive enough detect at distal enhancers. Here, we present analysis (BART), novel computational method software package predicting query or associate with genomic profile, based on more than 6000 existing ChIP-seq...
Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent classical factors. One such signal has been at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated polymorphism this region, rs12190287, resides the 3′ untranslated region (3′-UTR) TCF21, a basic-helix-loop-helix transcription factor, is predicted to alter seed binding sequence for miR-224. Allelic imbalance circulating leukocytes human artery...
Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via accumulation cholesterol inflammatory cells. However, recent evidence a substantial portion plaque may arise from subset "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in clonal fashion. Herein we use multicolor lineage-tracing models to confirm mature SMC can give rise...
Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes 9p21.3, human expression quantitative trait locus associated the tumor suppressor gene CDKN2B with risk haplotype, but its potential role pathobiology remains unclear.Here we used injury models found that Cdkn2b knockout mice displayed expected increase proliferation after injury,...
Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes basic-helix-loop-helix transcription factor believed serve critical role in development epicardial progenitor cells give rise artery smooth muscle (SMC) and cardiac fibroblasts. Using reporter gene immunolocalization with mouse human tissues we found vascular TCF21 expression adult is restricted primarily adventitial associated...
Abstract Aims Recent genome-wide association studies (GWAS) have identified that the JCAD locus is associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). However, mechanisms whereby candidate gene confers remain unclear. We addressed whether how affects development atherosclerosis, common cause CAD. Methods results By mining data in Genotype-Tissue Expression (GTEx) database, we found CAD-associated variants at are linked to increased expression human arteries,...
Rationale: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which majority these increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) critical in development They can play either beneficial or detrimental roles lesion pathogenesis, depending on nature their phenotypic changes. Objective: To identify genetic variants...
Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate disease. The role human-specific long noncoding RNAs in VSMC poorly understood.
Coronary artery disease (CAD) is the leading cause of death worldwide. Recent meta-analyses genome-wide association studies have identified over 175 loci associated with CAD. The majority these are in noncoding regions and predicted to regulate gene expression. Given that vascular smooth muscle cells (SMCs) play critical roles development progression CAD, we aimed identify subset CAD regulation transcription distinct SMC phenotypes.
While our understanding of the single-cell gene expression patterns underlying transformation vascular cell types during progression atherosclerosis is rapidly improving, clinical and pathophysiological relevance these changes remains poorly understood.
BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance human atherosclerosis still evolving. Intraplaque hemorrhage thought to be a major contributor plaque progression part by stimulating influx CD163 + macrophages. Here, we explored hypothesis that macrophages cause through induction proapoptotic endothelial-to-mesenchymal transition (EndMT) within...