Michael Alexanian
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View article: Targeting RUNX1 in Macrophages Facilitates Cardiac Recovery
Targeting RUNX1 in Macrophages Facilitates Cardiac Recovery Open
Despite advances in disease treatment, our understanding of how damaged organs recover and the mechanisms governing this process remain poorly defined. Here, we mapped the transcriptional and regulatory landscape of human cardiac recovery …
View article: BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression
BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression Open
BRD4 inhibition blocks stress-induced recruitment of pro-inflammatory monocytes to the heart. BRD4 inhibition reprograms resident cardiac macrophages toward a reparative phenotype marked by reduced NF-κB signaling and diminished MHC-II exp…
View article: Chromatin remodelling drives immune cell–fibroblast communication in heart failure
Chromatin remodelling drives immune cell–fibroblast communication in heart failure Open
View article: A genome-wide CRISPR screen identifies BRD4 as a regulator of cardiomyocyte differentiation
A genome-wide CRISPR screen identifies BRD4 as a regulator of cardiomyocyte differentiation Open
View article: Single-cell multimodal analyses reveal epigenomic and transcriptomic basis for birth defects in maternal diabetes
Single-cell multimodal analyses reveal epigenomic and transcriptomic basis for birth defects in maternal diabetes Open
View article: Chromatin Remodeling Drives Immune-Fibroblast Crosstalk in Heart Failure Pathogenesis
Chromatin Remodeling Drives Immune-Fibroblast Crosstalk in Heart Failure Pathogenesis Open
Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet the molecular mechanisms governing their crosstalk are poorly understood. In diseased organs, stress-induced changes in gene expression fu…
View article: Transcriptional plasticity of fibroblasts in heart disease
Transcriptional plasticity of fibroblasts in heart disease Open
Cardiac fibroblasts play an essential role in maintaining the structural framework of the heart. Upon stress, fibroblasts undergo a cell state transition to activated fibroblasts (also referred to as myofibroblasts), a highly synthetic cel…
View article: Targeting transcription in heart failure via CDK7/12/13 inhibition
Targeting transcription in heart failure via CDK7/12/13 inhibition Open
Heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, highlighting an urgent need for new therapeutic strategies. As stress-activated cardiac signaling cascades converge on the nucleus to drive maladaptive…
View article: Single Cell Multimodal Analyses Reveal Epigenomic and Transcriptomic Basis for Birth Defects in Maternal Diabetes
Single Cell Multimodal Analyses Reveal Epigenomic and Transcriptomic Basis for Birth Defects in Maternal Diabetes Open
Birth defects occur in ∼6% of all live births and can be caused by combinations of genetic and environmental influences 1 . Large-scale DNA sequencing efforts are revealing genetic influences 2,3 , but investigations into the contributions…
View article: Single Cell Epigenetics Reveal Cell-Cell Communication Networks in Normal and Abnormal Cardiac Morphogenesis
Single Cell Epigenetics Reveal Cell-Cell Communication Networks in Normal and Abnormal Cardiac Morphogenesis Open
Communication between myriad cell types during organ formation underlies proper morphogenesis 1 . In cardiac development, reciprocal signaling between mesoderm progenitors and neural crest cells is essential, and its disruption leads to co…
View article: KLF15 cistromes reveal a hepatocyte pathway governing plasma corticosteroid transport and systemic inflammation
KLF15 cistromes reveal a hepatocyte pathway governing plasma corticosteroid transport and systemic inflammation Open
Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are well understood, less is known about mechanisms controlli…
View article: Transcription factor protein interactomes reveal genetic determinants in heart disease
Transcription factor protein interactomes reveal genetic determinants in heart disease Open
View article: Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids
Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids Open
View article: A transcriptional switch governs fibroblast activation in heart disease
A transcriptional switch governs fibroblast activation in heart disease Open
View article: Integration of Protein Interactome Networks with Congenital Heart Disease Variants Reveals Candidate Disease Genes
Integration of Protein Interactome Networks with Congenital Heart Disease Variants Reveals Candidate Disease Genes Open
SUMMARY Congenital heart disease (CHD) is present in 1% of live births, yet identification of causal mutations remains a challenge despite large-scale genomic sequencing efforts. We hypothesized that genetic determinants for CHDs may lie i…
View article: Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity
Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity Open
View article: BRD4 (Bromodomain-Containing Protein 4) Interacts with GATA4 (GATA Binding Protein 4) to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes
BRD4 (Bromodomain-Containing Protein 4) Interacts with GATA4 (GATA Binding Protein 4) to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes Open
Background: Gene regulatory networks control tissue homeostasis and disease progression in a cell type–specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue specificit…
View article: BETs that cover the spread from acquired to heritable heart failure
BETs that cover the spread from acquired to heritable heart failure Open
Heart failure (HF) with reduced contractile function is a common and lethal syndrome in which the heart cannot pump blood to adequately meet bodily demands, resulting in high mortality despite the current standard of care. In modern societ…
View article: A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease
A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease Open
In diseased organs, stress-activated signaling cascades alter chromatin, triggering broad shifts in transcription and cell state that exacerbate pathology. Fibroblast activation is a common stress response that worsens lung, liver, kidney …
View article: Developmental co-emergence of cardiac and gut tissues modeled by human iPSC-derived organoids
Developmental co-emergence of cardiac and gut tissues modeled by human iPSC-derived organoids Open
During embryogenesis, paracrine signaling between tissues in close proximity contributes to the determination of their respective cell fate(s) and development into functional organs. Organoids are in vitro models that mimic organ formation…
View article: BRD4 Interacts with GATA4 to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes
BRD4 Interacts with GATA4 to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes Open
Gene regulatory networks control tissue plasticity during basal homeostasis and disease in a cell-type specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue-specificit…
View article: Long Noncoding RNAs in Cardiac Development
Long Noncoding RNAs in Cardiac Development Open
The exquisite transcriptional control of developmental gene programs is critical for hardwiring the complex expression patterns that govern cell-fate determination and differentiation during heart development. During the past several years…
View article: Integration of Protein Interactome Networks With Congenital Heart Disease Variants Reveals Candidate Disease Genes
Integration of Protein Interactome Networks With Congenital Heart Disease Variants Reveals Candidate Disease Genes Open
View article: Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation
Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation Open
Rationale: Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear wh…
View article: Conserved epigenetic regulatory logic infers genes governing cell identity
Conserved epigenetic regulatory logic infers genes governing cell identity Open
SUMMARY Determining genes orchestrating cell differentiation in development and disease remains a fundamental goal of cell biology. This study establishes a genome-wide metric based on the gene-repressive tri-methylation of histone 3 lysin…
View article: Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation
Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation Open
Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in pre-clinical models of heart failure (HF). However, the mechanisms by which BRD4 promotes pathological myocardial fibrosis re…
View article: The Cardiac Myofibroblast
The Cardiac Myofibroblast Open
View article: A transcribed enhancer dictates mesendoderm specification in pluripotency
A transcribed enhancer dictates mesendoderm specification in pluripotency Open
Enhancers and long noncoding RNAs (lncRNAs) are key determinants of lineage specification during development. Here, we evaluate remodeling of the enhancer landscape and modulation of the lncRNA transcriptome during mesendoderm specificatio…
View article: The long noncoding RNA <i>Wisper</i> controls cardiac fibrosis and remodeling
The long noncoding RNA <i>Wisper</i> controls cardiac fibrosis and remodeling Open
A super-enhancer–associated long noncoding RNA, Wisper , controls cardiac fibrosis and pathological remodeling in the damaged heart.
View article: The long noncoding RNA Wisper controls cardiac fibrosis and remodeling
The long noncoding RNA Wisper controls cardiac fibrosis and remodeling Open
Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of cardiac development and disease. However, our understanding of the importance of these molecules in cardiac fibrosis is limited. Using an integrated genomic screen, we id…