A5024125902- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Congenital Heart Disease Studies
- Tissue Engineering and Regenerative Medicine
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Connective Tissue Growth Factor Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Cardiovascular Effects of Exercise
- Virus-based gene therapy research
- Animal Genetics and Reproduction
- Pancreatic function and diabetes
- PARP inhibition in cancer therapy
- Coronary Artery Anomalies
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Liver physiology and pathology
- Cardiovascular Disease and Adiposity
Medical College of Wisconsin
2019-2024
Medical University of South Carolina
2020
University of Southern California
2017
Broad Center
2011-2015
Institute for Stem Cell Biology and Regenerative Medicine
2015
University of California, Los Angeles
2009-2013
Newcastle University
2013
Memorial Sloan Kettering Cancer Center
2008
McLean Hospital
2007-2008
Harvard University
2007
Abstract The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown be effective at generating motor neurons from human embryonic (hESCs), we found that once specified a neural lineage, iPS could differentiated form with similar efficiency as hESCs. Human iPS-derived appeared follow normal developmental progression associated neuron formation and possessed prototypical...
Significance A layer of fat surrounds the heart in most mammals, including humans. The biology this tissue has been speculated for centuries, but never subjected to experimental analysis because common model species are thought not have tissue. In study, we show that rodents cardiac fat, albeit a very specific location heart. We implicate origin from epicardium (the outer epithelium heart) and underlying mechanisms account its derivation. By comparing human mouse epicardial cells, provide an...
It is clear that neural differentiation from human pluripotent stem cells generates are developmentally immature. Here, we show the let-7 plays a functional role in developmental decision making of progenitors, controlling whether these make neurons or glia. Through gain- and loss-of-function studies on both tissue derived cells, our data specifically regulates this context by regulation key chromatin-associated protein, HMGA2. Furthermore, provide evidence let-7/HMGA2 circuit acts HES5,...
Somatic polyploidization, an adaptation by which cells increase their DNA content to support growth, is observed in many cell types, including cardiomyocytes. Although polyploidization believed be beneficial, progression a polyploid state often accompanied loss of proliferative capacity. Recent work suggests that genetics heavily influence cardiomyocyte ploidy. However, the developmental course cardiomyocytes reach final ploidy has only been investigated select backgrounds. Here, we assessed...
Understanding the mechanisms of amyloid-beta protein (Abeta) production and clearance in brain has been essential to elucidating etiology Alzheimer disease (AD). Chronically decreasing Abeta levels is an emerging therapeutic approach for AD, but no such disease-modifying agents have achieved clinical validation. Certain proteases are responsible catabolism vivo, some experimental evidence suggests they could be used as tools reduce AD. The objective this study was determine if enhancing by...
Linker histones are essential components of chromatin, but the distributions and functions many during cellular differentiation not well understood. Here, we show that H1.5 binds to genic intergenic regions, forming blocks enrichment, in differentiated human cells from all three embryonic germ layers stem cells. In cells, H1.5, H1.3, preferentially genes encode membrane membrane-related proteins. Strikingly, 37% target belong gene family clusters, groups homologous located proximity each...
The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development a cell-based replacement therapy Parkinson's disease. Using parthenogenetic primate cell line, we have generated that display persistent expression midbrain regional cell-specific transcription factors, which establish their proper allow survival. We show here transplantation restores motor function hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats. Exposure...
Inactivation of the DNA mismatch repair pathway manifests as microsatellite instability, an accumulation mutations that drives carcinogenesis. Here, we determined whether instability in acute myeloid leukemia and myelodysplastic syndrome correlated with chromosomal poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity through disruption function. Acute cell lines (n=12) primary samples (n=18), bone marrow mononuclear cells from high-risk patients (n=63) were profiled for using...
Injury to the newborn mouse heart is efficiently regenerated, but this capacity lost by one week after birth. We found that IGF2, an important mitogen in development, required for neonatal regeneration. IGF2 originates from endocardium/endothelium and transduced cardiomyocytes insulin receptor. Following injury on postnatal day 1, absence of abolished injury-induced cell cycle entry during early part first week. Consequently, regeneration failed despite later presence additional...
Abstract The clinical application of human-induced pluripotent stem cells (hiPSCs) requires not only the production Good Manufacturing Practice-grade (GMP-grade) hiPSCs but also derivation specified cell types for transplantation under GMP conditions. Previous reports have suggested that can be produced in absence animal-derived reagents (xenobiotics) to ease transition standards. However, facilitate use cell-based therapeutics, their progeny should xenobiotics conditions requiring extensive...
Recent evidence implicates mononuclear diploid cardiomyocytes as a proliferative and regenerative subpopulation of the postnatal heart. The number these is complex trait showing substantial natural variation among inbred mouse strains based on combined influences multiple polymorphic genes. One gene confirmed to influence this parameter cardiomyocyte-specific kinase Tnni3k. Here, we have studied Tnni3k alleles across species. Using newly-generated kinase-dead allele in mice, show that...
Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating progression. The literature suggests an important role for activation of interleukin-13 interleukin-4 signaling improving ischemic outcomes after myocardial infarction mice. Dupilumab, neutralizing antibody that inhibits shared IL13/IL4 receptor subunit IL4Rα, widely used conditions such as ectopic dermatitis...
ABSTRACT Sophisticated retargeting systems for lentiviral vectors have been developed in recent years. Most seek to suppress the viral envelope's natural tropism while modifying receptor-binding domain such that its is determined by specificity of engineered ligand-binding motif. Here we took advantage Nipah virus (NiV), whose attachment envelope glycoprotein has picomolar affinity ephrinB2, a molecule proposed as molecular marker “stemness” (present on embryonic, hematopoietic, and neural...
There is great interest in identifying signaling pathways that promote cardiac repair after myocardial infarction (MI). Prior studies suggest a beneficial role for IL-13 neonatal heart regeneration; however, the cell types mediating regeneration and extent of adult injury are unknown. We identified an abundant source related cytokine, IL-4, type 2 innate lymphoid cells, but this phenomenon declined precipitously hearts. Moreover, receptor deletion macrophages impaired function resulted...
Runx1 is sufficient but not required for cardiomyocyte cell cycle.
Most mouse cardiomyocytes (CMs) become multinucleated shortly after birth via endoreplication and interrupted mitosis, which persists through adulthood. The very closely related inbred strains BALB/cJ BALB/cByJ differ substantially (6.6% vs. 14.3%) in adult mononuclear CM level. This difference is the likely outcome of a single X-linked polymorphic gene that functions CM-nonautonomous manner, for allele recessive to BALB/cJ. From whole exome sequence we identified two new protein coding...