A5086646162- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Cardiac Fibrosis and Remodeling
- Virus-based gene therapy research
- Connective Tissue Growth Factor Research
- MicroRNA in disease regulation
- Muscle Physiology and Disorders
- Genetics and Neurodevelopmental Disorders
- Magnesium Alloys: Properties and Applications
- Mesenchymal stem cell research
- Advanced biosensing and bioanalysis techniques
- Electrospun Nanofibers in Biomedical Applications
- Circular RNAs in diseases
- RNA Research and Splicing
- Galectins and Cancer Biology
- Cardiomyopathy and Myosin Studies
- Epigenetics and DNA Methylation
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Function and Risk Factors
- GDF15 and Related Biomarkers
- Cardiac Structural Anomalies and Repair
- Tissue Engineering and Regenerative Medicine
- Multilevel Inverters and Converters
Cardiovascular Institute of the South
2024
Icahn School of Medicine at Mount Sinai
2016-2024
MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed multiple injections of antagomirs against enhance cardiac contractility function through restoration murine heart failure model. However, for clinical application, more stable suppressor would be desirable. Tough Decoy (TuD) inhibitors emerging as highly effective...
Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used modified mRNA (modRNA) gene delivery platform to deliver cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFβ, DN-Wnt8a, acid ceramidase (AC)-to induce CM-like cells. We showed...
Cytokine-like 1 (Cytl1) is a secreted protein that involved in diverse biological processes. A comparative modeling study indicated Cytl1 structurally and functionally similar to monocyte chemoattractant (MCP-1). As MCP-1 plays an important role cardiac fibrosis (CF) heart failure (HF), we investigated the of mouse model CF HF. was upregulated failing heart. Pressure overload-induced significantly attenuated cytl1 knock-out (KO) mice compared from wild-type (WT) mice. By contrast,...
Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) major disorder currently lacks curative treatment options, MI commonly accompanied by fibrosis impaired function. Our group previously matricellular protein CCN5 inhibits (CF)...
Directly injecting naked or lipid nanoparticle (LNP)-encapsulated modified mRNA (modRNA) allows rapid and efficient protein expression. This non-viral technology has been used successfully in modRNA vaccines against SARS-CoV-2. The main challenges using were the initial requirement for an ultra-cold storage to preserve their integrity concerns regarding unwanted side effects from this new technology. Here, we showed that maintains its when stored up 7 days at 4 °C, LNP-encapsulated room...
Highlights•Six1 is up-regulated in failing hearts.•Overexpression of Six1 leads to cardiac abnormalities vitro and vivo.•In stress conditions, directly binds the MCM7 promoter, inducing an elevation miR-25, which turn reduces SERCA2a.•In hearts, epigenetically regulated through PRC2 complex across species.AbstractThe reduced expression sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2a) a hallmark heart failure. We previously showed that miR-25 crucial transcriptional regulator SERCA2a heart....
Abstract Background Cardiac gene therapy using the adeno‐associated virus serotype 9 vector is widely used because of its efficient transduction. However, promoters to drive expression often cause off‐target localization. To overcome this, studies have applied cardiac‐specific promoters, although debilitated compared that ubiquitous promoters. address these issues in context atrial‐specific expression, an enhancer calsequestrin cis‐ regulatory module 4 ( CRM4 ) and highly promoter sarcolipin...
Abstract Atrial structural remodelling including atrial hypertrophy and fibrosis is a key mediator of fibrillation (AF). We previously demonstrated that the matricellular protein CCN5 elicits anti‐fibrotic anti‐hypertrophic effects in left ventricles under pressure overload. here determined utility ameliorating adverse arrhythmias murine model angiotensin II (AngII) infusion. Advanced was induced by AngII infusion control mice overexpressing either through transgenesis (CCN5 Tg) or...
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration due to dystrophin gene mutations. Patients with DMD initially experience weakness in their limbs during adolescence. With age, patients develop fatal respiratory and cardiac dysfunctions. During the later stages of disease, severe fibrosis occurs, compromising function. Previously, our research showed that matricellular protein CCN5 has antifibrotic properties. Therefore, we hypothesized...
Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, has potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) major disorder currently lacks curative treatment options. MI commonly accompanied by fibrosis impaired function. Our group previously demonstrated matricellular protein CCN5 inhibits...