A5102773074- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Peroxisome Proliferator-Activated Receptors
- Galectins and Cancer Biology
- Cardiomyopathy and Myosin Studies
- Connexins and lens biology
- Epigenetics and DNA Methylation
- Cardiac Ischemia and Reperfusion
- Cardiovascular Function and Risk Factors
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Lipid metabolism and biosynthesis
- Histone Deacetylase Inhibitors Research
- Cardiac electrophysiology and arrhythmias
- Fuel Cells and Related Materials
- Protein Tyrosine Phosphatases
- Cancer-related molecular mechanisms research
- Heat shock proteins research
- Plant and Fungal Interactions Research
- Viral Infectious Diseases and Gene Expression in Insects
- Sirtuins and Resveratrol in Medicine
- Receptor Mechanisms and Signaling
- Cardiac Fibrosis and Remodeling
Virginia Tech
2022-2024
Carilion Clinic
2023-2024
Biomedical Research Institute
2021-2024
University of Utah
2017-2023
Carilion Roanoke Memorial Hospital
2022-2023
Kumamoto University
2020-2022
Harrison Medical Center
2021
Continental (United States)
2017-2020
The heart utilizes multiple adaptive mechanisms to maintain pump function. Compensatory cardiac hypertrophy reduces wall stress and oxygen consumption, thereby protecting the against acute blood pressure elevation. nuclear effector of Hippo pathway, Yes-associated protein 1 (YAP), is activated mediates compensatory in response overload (PO). In this study, YAP promoted glycolysis by upregulating glucose transporter (GLUT1), which turn caused accumulation intermediates metabolites glycolytic,...
Significance Smyd1 is a muscle-specific histone methyltransferase, and its role in the regulation of growth differentiation skeletal cardiac muscle well established. However, despite persistent expression postnatal cardiomyocytes, adult heart largely unknown. We show that regulates energy metabolism heart. Cardiac-specific ablation mouse resulted global downregulation mitochondrial proteins involved oxidative phosphorylation, concurrent with reduced respiration capacity. further demonstrate...
Abstract In the past decade, many long noncoding RNAs (lncRNAs) have been identified and their in vitro functions defined, although some cases vivo remain less clear. Moreover, unlike nuclear lncRNAs, roles of cytoplasmic lncRNAs are defined. Here, using a gene trapping approach mouse embryonic stem cells, we identify Caren (short for cardiomyocyte-enriched transcript), lncRNA abundantly expressed cardiomyocytes. maintains cardiac function under pathological stress by inactivating ataxia...
Progressive age-induced deterioration in the structure and function of cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, endothelial dysfunction. These changes are driven by complex processes that interconnected, such as oxidative stress, mitochondrial autophagy, inflammation, telomere In recent years, advances research aging, including wide use animal models elucidated an abundance cell signaling pathways involved these...
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The Connexin43 gap junction gene GJA1 has one coding exon, but its mRNA undergoes internal translation to generate N-terminal truncated isoforms of with the predominant isoform being only 20 kDa in size (GJA1-20k). Endogenous GJA1-20k protein is not membrane bound and been found increase response ischemic stress, localize mitochondria, mimic preconditioning protection heart. However, it known how benefits mitochondria provide this protection. Here, using human cells mice, we identify that...
The transcriptional regulatory machinery in mitochondrial bioenergetics is complex and still not completely understood. We previously demonstrated that the histone methyltransferase Smyd1 regulates energetics. Here, we identified Perm1 (PPARGC-1 ESRR-induced regulator, muscle specific 1) as a downstream target of through RNA-seq. Chromatin immunoprecipitation assay showed directly interacts with promoter mouse heart, this interaction was significantly reduced hearts failing due to pressure...
PERM1 is a striated muscle-specific regulator of mitochondrial bioenergetics. We previously demonstrated that downregulated in the failing heart and positively regulates metabolic genes known as targets transcription factor ERRα its coactivator PGC-1α cultured cardiomyocytes. The aims this study were to determine effect loss on cardiac function energetics using newly generated Perm1-knockout (Perm1-/-) mice investigate molecular mechanisms transcriptional control.Echocardiography showed...
BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of expression is associated with cardiomyopathy mice, although its human unclear. This study aims to determine the impact loss-of-function variants on humans. METHODS: Individuals were identified and consented. Induced pluripotent stem cell–derived cardiomyocytes generated from proband hosting Q187X nonsense variant as an vitro model...
Background: Proper dynamics of RNA polymerase II, such as promoter recruitment and elongation, are essential for transcription. PGC-1α (peroxisome proliferator-activated receptor [PPAR]-γ coactivator-1α), also termed PPARGC1a, is a transcriptional coactivator that stimulates energy metabolism, target genes downregulated in the failing heart. However, whether dysregulation II occurs heart failure has not been defined. Methods Results: Chromatin immunoprecipitation-sequencing revealed reduced...
The tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production the healthy heart. However, heart failure, TCA becomes dysregulated. Understanding mechanism by which genes are transcribed is an important prerequisite to understanding how these become dysregulated failing PPARγ coactivator 1α (PGC-1α) transcriptional that broadly induces involved production. PGC-1α potentiates its effects through coactivation of coupled transcription factors, such as estrogen-related...
Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. Here, we show that gene delivery Perm1 via adeno-associated virus (AAV) simultaneously enhances cardiac biogenesis in C57BL6 mice. Moreover, found PERM1 interacts with Troponin C (TnC), a key contractile protein striated muscle, AAV- led to upregulation TnC. This study suggests may be novel therapeutic approach treat failure by restoring
The "stress" kinases cAMP-dependent protein kinase (PKA) and calcium/calmodulin-dependent II (CaMKII), phosphorylate the Na
Isoproterenol-induced amylase release from rabbit parotid acini was examined in relation to cyclic AMP (cAMP) concentrations, cAMP-dependent protein kinase (cAMP-PK) activity ratios and phosphorylation. Initial stimulation of by isoproterenol preceded increases cAMP, cAMP-PK phosphorylation a 34,000 MW (major) 30,000 (minor) the microsomal fraction. When propranolol added, decreases cAMP concentrations reduction release. Detailed analysis performed on protein. The dephosphorylation 34...
A prominent theory of cell death in myocardial ischemia/reperfusion (I/R) posits that the primary and pivotal step irreversible injury is opening mitochondrial permeability transition (MPT) pore. However, predominantly positive evidence protection against infarct afforded by MPT inhibitor, Cyclosporine (CsA), experimental studies stark contrast with overall lack benefit found clinical trials CsA. One reason for discrepancy might be fact relatively short ischemic episodes (<1 hour) do not...
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Heart failure remains the leading cause of death in U.S., and 50% patients with heart still die within 5 years after diagnosis. Mitochondrial impairment contractile dysfunction are hallmarks reduced ejection fraction (HFrEF). Yet, there is currently no therapeutic strategy targeting both mitochondria muscle contractility. PERM1 a striated-muscle-specific regulator mitochondrial bioenergetics predominantly expressed skeletal muscle. Our recent studies demonstrated that downregulated human...
Abstract We and others demonstrated that PERM1 is a positive regulator of mitochondrial bioenergetics in the heart. However, discrepant results have emerged with regard to whether loss-of-function affect cardiac contractility. In order exclude possibility reported negative can be due insufficient power statistical test, we conducted more robust echocardiography (Echo) analysis by increasing sample size. used Perm1 -KO their respective wildtype (WT) littermates, which were destined tissue...