A5010728753- Congenital heart defects research
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Nuclear Structure and Function
- Peroxisome Proliferator-Activated Receptors
- Developmental Biology and Gene Regulation
- Cardiomyopathy and Myosin Studies
- Coronary Artery Anomalies
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Cardiovascular Effects of Exercise
- Fuel Cells and Related Materials
- Pancreatic function and diabetes
- Cardiovascular Function and Risk Factors
- Congenital Heart Disease Studies
Icahn School of Medicine at Mount Sinai
2017-2023
Child Health and Development Institute
2020-2022
Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via silencing. Unlike many histone modifications chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human types, which limits our understanding role peripheral plays development disease.
Zebrafish can efficiently regenerate their heart through cardiomyocyte proliferation. In contrast, mammalian cardiomyocytes stop proliferating shortly after birth, limiting the regenerative capacity of postnatal heart. Therefore, if endogenous potential proliferation could be enhanced, it offer a promising future therapy for failure patients. Here, we set out to systematically identify small molecules triggering By screening chemical compound libraries utilizing Fucci-based system assessing...
Abstract During development multiple progenitor populations contribute to the formation of four-chambered heart and its diverse lineages. However, underlying mechanisms that result in specification these are not yet fully understood. We have previously identified a population cells gives rise selectively ventricles but atria. Here, we used this knowledge transcriptionally profile subsets cardiac mesoderm from mouse embryo an enrichment for Notch signaling components ventricular progenitors....
Abstract Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via silencing. Unlike many histone modifications chromatin-associated proteins, lamin-associated domains (LADs) have yet be mapped genome-wide in diverse panel human types, which limited our understanding role peripheral plays development disease. To address this gap, we LAMIN B1 (LB1) across twelve...
ABSTRACT While much progress has been made in understanding early cardiac development, the precise mechanisms that specify different cardiomyocyte subtypes remain poorly understood. Recent data from our lab have shown transient Foxa2 expression identifies a progenitor population with exclusive ventricular differentiation potential mouse heart. Here we translated this concept to human pluripotent stem cell (hPSC) system. Using FOXA2-GFP reporter line characterized of FOXA2 during hPSC and...
Background: Heart failure (HF) is a complex clinical condition associated with substantial morbidity and mortality worldwide. The contractile dysfunction arrhythmogenesis related to HF has been linked the remodelling of calcium (Ca ++ ) handling. Phospholamban (PLN) emerged as key regulator intracellular Ca concentration. Of PLN mutations, L39X intriguing it not fully characterized. This mutation believed be functionally equivalent null (KO) but contrary KO mice, carriers develop lethal...
Background: Defective calcium (Ca++) handling is a hallmark of HF across species. Together with the Sarco/Endoplasmic Reticulum Ca-ATPase (SERCA2a), Phospholamban (PLN) has emerged as critical regulator Ca++homeostasis. Worldwide, PLN mutations are identified increasing frequency in patients dilated, hypertrophic and arrhythmogenic cardiomyopathy (CMPs) but causative defects leading to CMP remain incompletely understood. While preclinical studies have unequivocally shown that absence (PLNKO)...
SUMMARY Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease. A major caveat however is that they remain functionally structurally immature in culture, limiting their potential for disease modeling regenerative approaches. Here, we address the question of how different metabolic pathways can be modulated order induce efficient hPSC-CM maturation. We show PPAR signaling acts isoform-specific manner balance...