Eric M. Small
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View article: Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction
Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction Open
The Slit2 guidance ligand and its Roundabout (Robo) family of receptors regulate axonal guidance and vascular patterning during cardiac morphogenesis, yet the role of Slit2-Robo signaling in the adult heart remains unclear. Here, we identi…
View article: Epicardial contributions to fibro-inflammatory signaling in a Pkp2-deficient arrhythmogenic cardiomyopathy model
Epicardial contributions to fibro-inflammatory signaling in a Pkp2-deficient arrhythmogenic cardiomyopathy model Open
Background Arrhythmogenic Cardiomyopathy (ACM) is an inherited disease that is characterized by lethal ventricular arrhythmias stemming from myocyte dysfunction. ACM is associated with considerable subepicardial fibrosis and inflammation w…
View article: Deletion of RSK2 kinase alleviates age-dependent hypertension
Deletion of RSK2 kinase alleviates age-dependent hypertension Open
Background Hypertension prevalence increases with age, reaching over 70% of people over age 65. The underlying mechanisms are poorly understood. This study interrogates a new signaling pathway in vascular smooth muscle of aged mice driven …
View article: Whole genome transcriptomics reveal distinct atrial versus ventricular responses to neonatal hyperoxia
Whole genome transcriptomics reveal distinct atrial versus ventricular responses to neonatal hyperoxia Open
Preterm infants often require oxygen (hyperoxia) at birth, but early exposure increases the risk of heart failure later in life. Previously, we showed neonatal mice exposed to hyperoxia develop adult diastolic dysfunction and heart failure…
View article: PERCEPTIVE: an R Shiny pipeline for the prediction of epigenetic modulators in novel species
PERCEPTIVE: an R Shiny pipeline for the prediction of epigenetic modulators in novel species Open
Epigenetic processes play key roles in regulating gene expression, genome stability, and metabolic output in organisms across the tree of life. Yet, the role epigenetics plays in regulating genomes and behaviors remains underdeveloped for …
View article: FZD2 inhibits YAP and prevents cell cycle reentry in adult murine cardiomyocytes
FZD2 inhibits YAP and prevents cell cycle reentry in adult murine cardiomyocytes Open
Rationale Fully differentiated cardiomyocytes (CMs) are post-mitotic and cannot repopulate damaged tissue after myocardial infarction (MI). Understanding the mechanisms preventing CM proliferation or promoting their survival after injury m…
View article: Epigenomic manipulation reveals the relationship between locus specific chromatin dynamics and gene expression
Epigenomic manipulation reveals the relationship between locus specific chromatin dynamics and gene expression Open
Summary Dysregulation of epigenetic processes leads to a plethora of abnormalities including disease states such as cancer. Therapies focused on epigenetic modulation alter gene expression to correct dysfunction, though the mechanisms and …
View article: Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression
Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression Open
Genomic DNA folds into complex configurations that produce particular local and global structures thought to profoundly impact genome function. To understand the dynamic nature of this relationship, we investigated the extent of host chrom…
View article: p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload
p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload Open
BACKGROUND: Cardiomyopathy is characterized by the pathological accumulation of resident cardiac fibroblasts that deposit ECM (extracellular matrix) and generate a fibrotic scar. However, the mechanisms that control the timing and extent o…
View article: Cardiac pericytes mediate the remodeling response to myocardial infarction
Cardiac pericytes mediate the remodeling response to myocardial infarction Open
Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and…
View article: SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes
SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes Open
Background: Heart failure with preserved ejection fraction (HFpEF) is a growing health problem without effective therapies. Epidemiological studies indicate that diabetes is a strong risk factor for HFpEF, and about 45% of patients with HF…
View article: Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC
Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC Open
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside i…
View article: Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics
Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics Open
The neonatal mammalian heart exhibits a remarkable regenerative potential, which includes fibrotic scar resolution and the generation of new cardiomyocytes. To investigate the mechanisms facilitating heart repair after apical resection in …
View article: Myocardin is sufficient and necessary for cardiac gene expression in Xenopus
Myocardin is sufficient and necessary for cardiac gene expression in Xenopus Open
Myocardin is a cardiac- and smooth muscle-specific cofactor for the ubiquitous transcription factor serum response factor (SRF). Using gain-of-function approaches in the
View article: Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin
Prevention of Fibrosis and Pathological Cardiac Remodeling by Salinomycin Open
Rationale: Cardiomyopathy is characterized by the deposition of extracellular matrix by activated resident cardiac fibroblasts called myofibroblasts. There are currently no therapeutic approaches to blunt the development of pathological fi…
View article: Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling
Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling Open
Significance Mature cardiomyocytes are highly adapted to pump efficiently over billions of cycles. The mechanisms that regulate and coordinate the acquisition of the specialized features of mature cardiomyocytes in the postnatal period are…
View article: The Role of the Epicardium During Heart Development and Repair
The Role of the Epicardium During Heart Development and Repair Open
The heart is lined by a single layer of mesothelial cells called the epicardium that provides important cellular contributions for embryonic heart formation. The epicardium harbors a population of progenitor cells that undergo epithelial-t…
View article: A Novel Role of Cyclic Nucleotide Phosphodiesterase 10A in Pathological Cardiac Remodeling and Dysfunction
A Novel Role of Cyclic Nucleotide Phosphodiesterase 10A in Pathological Cardiac Remodeling and Dysfunction Open
Background: Heart failure is a leading cause of death worldwide. Cyclic nucleotide phosphodiesterases (PDEs), through degradation of cyclic nucleotides, play critical roles in cardiovascular biology and disease. Our preliminary screening s…
View article: Sarcomeres regulate cardiomyocyte maturation through MRTF-SRF signaling
Sarcomeres regulate cardiomyocyte maturation through MRTF-SRF signaling Open
Cardiomyocyte maturation is essential for robust heart contraction throughout life. The signaling networks governing cardiomyocyte maturation remain poorly defined. Our prior studies established the transcription factor SRF as a key regula…
View article: Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts
Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts Open
Background Heart failure (HF) is invariably accompanied by development of cardiac fibrosis, a form of scarring that increases muscular tissue rigidity and decreases cardiac contractility. Cardiac fibrosis arises from a pathological attempt…
View article: Platelet-derived β2M regulates monocyte inflammatory responses
Platelet-derived β2M regulates monocyte inflammatory responses Open
β-2 Microglobulin (β2M) is a molecular chaperone for the major histocompatibility class I (MHC I) complex, hemochromatosis factor protein (HFE), and the neonatal Fc receptor (FcRn), but β2M may also have less understood chaperone-independe…