A5075487555- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Cardiomyopathy and Myosin Studies
- Virus-based gene therapy research
- Cardiovascular Effects of Exercise
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Congenital Heart Disease Studies
- Renal and related cancers
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Extracellular vesicles in disease
- Genomics and Chromatin Dynamics
- Genetics and Physical Performance
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Electrospun Nanofibers in Biomedical Applications
- Pancreatic function and diabetes
- Gene Regulatory Network Analysis
- Neuroscience and Neural Engineering
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- NF-κB Signaling Pathways
Icahn School of Medicine at Mount Sinai
2016-2025
Child Health and Development Institute
2014-2024
Mount Sinai Hospital
2024
New York Stem Cell Foundation
2024
University Health Network
2008-2017
Princess Margaret Cancer Centre
2017
University of Toronto
2017
Stem Cell Institute
2017
RELX Group (United States)
2017
Toronto Public Health
2011-2012
Significance Robust and predictive in vitro models of human cardiac tissue function could have transformative impact on our ability to test new drugs understand disease. Despite significant effort, the generation high-fidelity adult-like analogs remains challenging. In this paper, we systematically explore design criteria for pluripotent stem cell-derived engineered tissue. Parameters such as biomechanical stress during remodeling, input-cell composition, electrical stimulation, geometry are...
Adeno-associated virus (AAV) has emerged as one of the best tools for cardiac gene delivery due to its cardiotropism, long-term expression, and safety. However, a significant challenge successful clinical use is preexisting neutralizing antibodies (NAbs), which bind free AAVs, prevent efficient transduction, reduce or negate therapeutic effects. Here we describe extracellular vesicle-encapsulated AAVs (EV-AAVs), secreted naturally by AAV-producing cells, superior vector that delivers more...
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.
Here we describe the generation of Nes-Cre1 transgenic mouse line in which Cre recombinase expression is controlled by rat nestin promoter and intron 2 enhancer. This has previously been used for conditional loss-of-function studies various genes central nervous system first branchial arch ectoderm. report detailed temporal spatial recombination pattern using three different reporters Cre-mediated recombination, ROSA26R (R26R), Z/AP, Z/EG. Cre/loxP was detected embryos as early head-fold...
Sphingolipids have recently emerged as a biomarker of recurrence and mortality after myocardial infarction (MI). The increased ceramide levels in mammalian heart tissues during acute MI, demonstrated by several groups, is associated with higher cell death rates the left ventricle deteriorated cardiac function. Ceramidase, only enzyme known to hydrolyze proapoptotic ceramide, generates sphingosine, which then phosphorylated sphingosine kinase produce prosurvival molecule...
Modified mRNA (modRNA) is a new technology in the field of somatic gene transfer that has been used for delivery genes into different tissues, including heart. Our group and others have shown modRNAs injected heart are robustly translated encoded protein can potentially improve outcome injury models. However, optimal compositions modRNA reagents necessary to achieve expression not characterized yet. In this study, our aim was elucidate those parameters by testing nucleotide modifications,...
In self-renewing tissues such as the skin epidermis and bone marrow, Myc proteins control differentiation of stem cells proliferation progenitor cell types. epithelium small intestine, we show that c-Myc N-Myc are expressed in a differential manner. Whereas is proliferating transient-amplifying compartment crypts, restricted to differentiated villus single located near crypt base. has been implicated critical target canonical Wnt pathway, which essential for formation maintenance intestinal...
The c-Myc protein has been implicated in playing a pivotal role regulating the expression of large number genes involved many aspects cellular function. Consistent with this view, embryos lacking c-myc gene exhibit severe developmental defects and die before midgestation. Here, we show that Sox2Cre-mediated deletion conditional c-myc(flox) allele specifically epiblast (hence trophoectoderm primitive endoderm structures are wild type) rescues majority abnormalities previously characterized...
The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding cardiac development. However, mechanisms direct atrial versus ventricular specification remain largely unknown. Here we report population gives rise primarily cardiovascular cells ventricles only few (<5%) differentiated heart. These progenitors are specified during gastrulation, when they transiently express Foxa2,...
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...
The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This mechanistically linked p21(Cip1), which induced in tumors by the activated Ras-ERK pathway but repressed c-Myc. Acute elimination of established leads up-regulation lacking both p21(Cip1) reacquires normal...
The use of human stem cell-derived cardiomyocytes to study atrial biology and disease has been restricted by the lack a reliable method for cell labeling purification. goal this was generate an atrial-specific reporter construct identify purify atrial-like cardiomyocytes. We have created bacterial artificial chromosome (BAC) in which fluorescence is driven expression gene sarcolipin (SLN). When purified using flow cytometry, cells with high specifically express genes display functional...
Millions suffer from incurable lung diseases, and the donor shortage hampers organ transplants. Generating whole in conjunction with thymus is a significant milestone for transplantation because central to educate immune cells. Using lineage-tracing mice human pluripotent stem cell (PSC)-derived lung-directed differentiation, we revealed that gastrulating Foxa2 lineage contributed both mesenchyme epithelium formation. Interestingly, lineage-derived cells progressively increased occupied more...
Background/Objectives: Modified messenger RNA (modRNA) is a promising gene delivery method used to upregulate genes in cardiac tissue, with applications both clinical and preclinical settings prevent remodeling after ischemic injury. The 5′ untranslated region (5′UTR) plays crucial role regulating the translation efficiency of mRNA into functional proteins. Due high production cost short half-life modRNA, it essential identify novel 5′UTR designs that enhance modRNA heart. Methods: Here, we...
Membrane proteins are crucial to heart function and development. Here we combine cationic silica-bead coating with shotgun proteomics enrich for identify plasma membrane-associated from primary mouse neonatal human fetal ventricular cardiomyocytes. We Tmem65 as a cardiac-enriched, intercalated disc protein that increases during development in both hearts. Functional analysis of vitro using lentiviral shRNA-mediated knockdown cardiomyocytes vivo morpholino-based zebrafish show marked...
A library of well-characterized human induced pluripotent stem cell (hiPSC) lines from clinically healthy subjects could serve as a useful resource normal controls for in vitro development, disease modeling, genotype-phenotype association studies, and drug response evaluation. We report generation extensive characterization gender-balanced, racially/ethnically diverse hiPSC 40 individuals who range age 22 to 61 years. The hiPSCs match the karyotype short tandem repeat identities their...
Despite the diverse developmental origins of vascular smooth muscle cells (VSMCs), recent attempts to generate VSMCs from human embryonic stem (hESCs) differentiated along various lineages did not yield distinct cell phenotypes. The aim this study was derive and characterize functional coronary-like hESCs using serum-free cardiac-directed differentiation. Embryoid bodies (EBs) three pluripotent lines subjected differentiation in defined media were characterized over 30 days for VSMC-specific...