A5071723974- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Signaling Pathways in Disease
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Zebrafish Biomedical Research Applications
- Mechanical Circulatory Support Devices
- Viral Infections and Immunology Research
- Angiogenesis and VEGF in Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Fuel Cells and Related Materials
- Cardiac Structural Anomalies and Repair
- Kawasaki Disease and Coronary Complications
- Pluripotent Stem Cells Research
- Lymphatic System and Diseases
- Phagocytosis and Immune Regulation
- Sarcoidosis and Beryllium Toxicity Research
- Congenital Heart Disease Studies
- Transplantation: Methods and Outcomes
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Cardiac and Coronary Surgery Techniques
- Vasculitis and related conditions
- Cardiomyopathy and Myosin Studies
Washington University in St. Louis
2019-2025
Cincinnati Children's Hospital Medical Center
2015-2022
University of Cincinnati
2022
Recent advancements have brought to light the origins, complexity, and functions of tissue-resident macrophages. However, in context tissue injury or disease, large numbers monocytes infiltrate heart are thought contribute adverse remodeling failure pathogenesis. Little is understood about diversity monocyte-derived macrophages recruited after myocardial injury, including mechanisms that regulate monocyte recruitment fate specification.We sought test hypothesis distinct subsets CCR2- (C-C...
Heart failure represents a major cause of morbidity and mortality worldwide. Single-cell transcriptomics have revolutionized our understanding cell composition associated gene expression. Through integrated analysis single-cell single-nucleus RNA-sequencing data generated from 27 healthy donors 18 individuals with dilated cardiomyopathy, here we define the failing human heart. We identify cell-specific transcriptional signatures age heart reveal emergence disease-associated states. Notably,...
Recent studies have established that CCR2 (C-C chemokine receptor type 2) marks proinflammatory subsets of monocytes, macrophages, and dendritic cells contribute to adverse left ventricle (LV) remodeling heart failure progression. Elucidation the effector mechanisms mediate effects
Effective tissue repair after myocardial infarction entails a vigorous angiogenic response, guided by incompletely defined immune cell–endothelial cell interactions. We identify the monocyte- and macrophage-derived cytokine METRNL (meteorin-like) as driver of postinfarction angiogenesis high-affinity ligand for stem factor receptor KIT (KIT tyrosine kinase). mediated effects in cultured human endothelial cells through KIT-dependent signaling pathways. In mouse model infarction, promoted...
Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise granuloma remain unresolved. Furthermore, it unclear how cellular and transcriptomic landscape differs from other inflammatory heart diseases.
Cellular rejection after heart transplantation imparts significant morbidity and mortality. Current immunosuppressive strategies are imperfect, target recipient T cells, have adverse effects. The innate immune response plays an essential role in the recruitment activation of cells. Targeting donor would represent earliest interventional opportunity within cascade. There is limited knowledge about cell types functions setting cardiac transplantation, no current therapeutics exist for...
Inflammation and tissue fibrosis co-exist are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored there currently no therapeutics target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, chromatin accessibility profiling 38 donors, acutely infarcted, chronically failing hearts. We identified a disease-associated fibroblast trajectory marked by cell surface...
Abstract Cell fate decisions involved in vascular and hematopoietic embryonic development are still poorly understood. An ETS transcription factor Etv2 functions as an evolutionarily conserved master regulator of vasculogenesis. Here we report a single-cell transcriptomic analysis hematovascular wild-type etv2 mutant zebrafish embryos. Distinct transcriptional signatures different types progenitors identified using ci32Gt gene trap line, which the Gal4 activator is integrated into locus. We...
Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm migrate to midline where they coalesce form cardiac tube. acquire a molecular identity from other vascular endothelial cells initiate expression specific genes such as nfatc1. Yet pathways tissue interactions involved establishing endocardial are poorly understood. The endocardium develops tight association with cardiomyocytes. To test for potential role myocardium morphogenesis, we...
Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune promotes injury, the role of signaling tissue-resident context inflammation remains poorly understood. Here, we used a cardiac transplantation model dissect how Trem1/3 expression heart-resident regulates inflammation. is C-C chemokine 2...
Abstract Cardiac fibrosis is causally linked to heart failure pathogenesis and adverse clinical outcomes. However, the precise fibroblast populations that drive in human mechanisms govern their emergence remain incompletely defined. Here, we performed Cellular Indexing of Transcriptomes Epitomes by sequencing (CITE-seq) 22 explanted hearts from healthy donors, acute myocardial infarction (MI), chronic ischemic non-ischemic cardiomyopathy patients. We identified a trajectory marked activator...
Abstract Inflammation contributes to the pathogenesis of myocardial infarction and heart failure represents a viable therapeutic target. Monocytes their progeny are highly abundant display incredible functional diversity, serving as key determinants inflammation tissue repair. Much remains be learned regarding mechanisms signaling events that instruct monocyte fate decisions. We devised genetic lineage tracing strategy using Ccr2 crERT2 Rosa26 LSL-tdTomato mice in combination with single...
Chronic immunopathology contributes to the development of heart failure after a myocardial infarction. Both T and B cells adaptive immune system are present in myocardium have been suggested be involved post-MI immunopathology.
Tissue-resident macrophages are increasingly recognized as important determinants of organ homeostasis, tissue repair, remodeling and regeneration. Although the ontogeny function tissue-resident has been identified distinct from postnatal hematopoiesis, inability to specify, in vitro, similar populations that recapitulate these developmental waves limited our ability study their potential for regenerative applications. We took advantage concept monocyte-derived originate extra-embryonic...
Abstract Recovery of cardiac function is the ultimate goal heart failure therapy. Unfortunately, recovery remains a rare and poorly understood phemomenon. Herein, we performed single nucleus RNA-sequencing (snRNA-seq) from non-diseased donors patients. By comparing patients who recovered LV systolic following assist device implantation to those did not recover donors, defined cellular transcriptional landscape predictors recovery. We sequenced 40 hearts 185,881 nuclei with 13 distinct cell...
ABSTRACT Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms intellectual frequently have genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components TATA-binding protein associated factors (TAFs) recently been identified subset patients with disability, craniofacial hypoplasia, congenital heart disease. This syndrome has termed as TAFopathy includes mutations TATA binding...
Abstract Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia reperfusion injury, monocytes enter the differentiate into diverse subpopulations of macrophages. The mechanisms dynamics monocyte differentiation within this context are unknown. We investigated role macrophage hypoxia sensing on following reperfused infarction. show that deletion Hif1α , a response transcription factor, in resident macrophages led...
Inflammation and tissue fibrosis co-exist are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored, there currently no approved treatments that directly target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, chromatin accessibility profiling 45 donors, acutely infarcted, chronically failing hearts. We identified a disease-associated fibroblast trajectory...