Charles E. Murry
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View article: Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and the<i>TTN</i>RNA
Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and the<i>TTN</i>RNA Open
Eukaryotic nuclei adopt a highly compartmentalized architecture that influences nearly all genomic processes. Understanding how this architecture impacts gene expression has been hindered by a lack of tools for elucidating the molecular in…
View article: Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF
Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF Open
BACKGROUND: Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood. METH…
View article: Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies
Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies Open
Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cas…
View article: Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies (Adv. Sci. 24/2024)
Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies (Adv. Sci. 24/2024) Open
Injectable Cell Therapies Single‐component protein hydrogels assembled through homopentameric coiled‐coil bundling exhibit rapid shear thinning and self‐healing, protecting and sustaining viability of encapsulated cells through culture, in…
View article: Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies
Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies Open
While direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protecti…
View article: Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium
Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium Open
Human induced pluripotent stem cells (hiPSCs) offer opportunities to study human biology where primary cell types are limited. CRISPR technology allows forward genetic screens using engineered Cas9-expressing cells. Here, we sought to gene…
View article: Quiescent-yet-excitable pluripotent stem cell-derived cardiomyocytes engraft without fatal arrhythmias in minipig and primates
Quiescent-yet-excitable pluripotent stem cell-derived cardiomyocytes engraft without fatal arrhythmias in minipig and primates Open
Background Pluripotent stem cell-derived cardiomyocyte (PSC-CM) transplantation is a promising therapy for subacute myocardial infarction (MI), but transient engraftment-related arrhythmia (EA) is major barrier to clinical development (1, …
View article: Multiplexed functional assessments of<i>MYH7</i>variants in human cardiomyocytes at scale
Multiplexed functional assessments of<i>MYH7</i>variants in human cardiomyocytes at scale Open
Background Single, autosomal-dominant missense mutations in MYH7 , which encodes a sarcomeric protein (MHC-β) in cardiac and skeletal myocytes, are a leading cause of hypertrophic cardiomyopathy and are clinically-actionable. However, ∼75%…
View article: WITHDRAWN: Cell based dATP delivery as a therapy for chronic heart failure
WITHDRAWN: Cell based dATP delivery as a therapy for chronic heart failure Open
Withdrawal Statement The authors have withdrawn this manuscript because the senior authors have identified inconsistencies in the data presented in this manuscript, which affect the reliability of the main conclusions. In keeping with our …
View article: Graft–host coupling changes can lead to engraftment arrhythmia: a computational study
Graft–host coupling changes can lead to engraftment arrhythmia: a computational study Open
After myocardial infarction (MI), a significant portion of heart muscle is replaced with scar tissue, progressively leading to heart failure. Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CM) offer a promising option for improvi…
View article: CRaTER enrichment for on-target gene editing enables generation of variant libraries in hiPSCs
CRaTER enrichment for on-target gene editing enables generation of variant libraries in hiPSCs Open
Standard transgenic cell line generation requires screening 100-1000s of colonies to isolate correctly edited cells. We describe CRISPRa On-Target Editing Retrieval (CRaTER) which enriches for cells with on-target knock-in of a cDNA-fluore…
View article: Cardiomyocyte Apoptosis Is Associated with Contractile Dysfunction in Stem Cell Model of MYH7 E848G Hypertrophic Cardiomyopathy
Cardiomyocyte Apoptosis Is Associated with Contractile Dysfunction in Stem Cell Model of MYH7 E848G Hypertrophic Cardiomyopathy Open
Missense mutations in myosin heavy chain 7 (MYH7) are a common cause of hypertrophic cardiomyopathy (HCM), but the molecular mechanisms underlying MYH7-based HCM remain unclear. In this work, we generated cardiomyocytes derived from isogen…
View article: Engineered tissue vascularization and engraftment depends on host model
Engineered tissue vascularization and engraftment depends on host model Open
Developing vascular networks that integrate with the host circulation and support cells engrafted within engineered tissues remains a key challenge in tissue engineering. Most previous work in this field has focused on developing new metho…
View article: CRaTER enrichment for on-target gene-editing enables generation of variant libraries in hiPSCs
CRaTER enrichment for on-target gene-editing enables generation of variant libraries in hiPSCs Open
SUMMARY Standard transgenic cell line generation requires screening 100-1000s of colonies to isolate correctly edited cells. We describe CR ISPR a On- T arget E diting R etrieval (CRaTER) which enriches for cells with on-target knock-in of…
View article: Cardiomyocyte apoptosis contributes to contractile dysfunction in stem cell model of<i>MYH7</i>E848G hypertrophic cardiomyopathy
Cardiomyocyte apoptosis contributes to contractile dysfunction in stem cell model of<i>MYH7</i>E848G hypertrophic cardiomyopathy Open
Missense mutations in myosin heavy chain 7 ( MYH7 ) are a common cause of hyper-trophic cardiomyopathy (HCM), but the molecular mechanisms underlying MYH7 -based HCM remain unclear. In this work, we generated cardiomyocytes derived from is…
View article: Lessons learnt, and still to learn, in first in human stem cell trials
Lessons learnt, and still to learn, in first in human stem cell trials Open
Developing cellular therapies is not straightforward. This Perspective summarizes the experience of a group of academic stem cell investigators working in different clinical areas and aims to share insight into what we wished we knew befor…
View article: Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation
Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation Open
Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. The gene-regulatory mechanisms underpinning endothelial specialization are largely unknown, as are the roles o…
View article: dATP Elevation Induces Myocardial Metabolic Remodeling to Support Improved Cardiac Function
dATP Elevation Induces Myocardial Metabolic Remodeling to Support Improved Cardiac Function Open
Hallmark features of systolic heart failure are reduced contractility and impaired metabolic flexibility of the myocardium. Cardiomyocytes (CMs) with elevated deoxy ATP (dATP) via overexpression of ribonucleotide reductase (RNR) enzyme rob…
View article: Perpendicular Shear Stresses Drive Transmural Helical Remodeling in Engineered Human Ventricular Models
Perpendicular Shear Stresses Drive Transmural Helical Remodeling in Engineered Human Ventricular Models Open
Tissue engineering with human induced pluripotent stem cell-derived cardiomyocytes enables unique opportunities for creating physiological models of the heart in vitro. However, there are few approaches available that can recapitulate the …