A5002417073- Cardiac Fibrosis and Remodeling
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Single-cell and spatial transcriptomics
- Coronary Interventions and Diagnostics
- Mechanical Circulatory Support Devices
- Signaling Pathways in Disease
- Cardiovascular Function and Risk Factors
- Viral Infections and Immunology Research
- Transplantation: Methods and Outcomes
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- Cardiac Structural Anomalies and Repair
- Cardiac Valve Diseases and Treatments
- Immune Cell Function and Interaction
- Aortic aneurysm repair treatments
- Cardiac and Coronary Surgery Techniques
- Extracellular vesicles in disease
- CRISPR and Genetic Engineering
- Fuel Cells and Related Materials
- Infective Endocarditis Diagnosis and Management
- Gene expression and cancer classification
- Antiplatelet Therapy and Cardiovascular Diseases
Washington University in St. Louis
2020-2025
Amgen (United States)
2024-2025
University of Missouri–St. Louis
2024
California Institute of Technology
2017-2020
Massachusetts Institute of Technology
2018-2020
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,...
Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 death-ligand 1) or CTLA4 (cytotoxic T-lymphocyte-associated 4), have revolutionized cancer management but are associated with devastating immune-related adverse events including myocarditis. The main risk factor for ICI myocarditis is the use of combination and inhibition. often fulminant pathologically characterized by myocardial infiltration T lymphocytes macrophages. Although much has...
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...
Tissue-resident macrophages are complementary to proinflammatory promote the progression of atherosclerosis. The noninvasive detection their presence and dynamic variation will be important understanding role in pathogenesis goal this study was develop a targeted PET radiotracer for imaging CD163-positive (CD163+) multiple mouse atherosclerosis models assess potential CD163 as biomarker humans. <b>Methods:</b> CD163-binding peptide identified using phage display conjugated with NODAGA...
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...
BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine pathology and possible treatment strategies. We sought establish a high-throughput approach for echocardiography-guided induction ischemia/reperfusion (IR) in mice. METHODS: After visualization the left coronary artery high-resolution ultrasound imaging echocardiographic definition level occlusion, anterior descending was temporarily occluded 2 micromanipulator-controlled needles....
Abstract SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between cell activation of the peripheral compartment and survival critical COVID-19 remains to be established. Here we use single-cell RNA sequencing Cellular Indexing Transcriptomes Epitomes by sequence mapping elucidate type specific transcriptional signatures that associate with predict COVID-19. Patients who survive infection display antibody processing, early...
Abstract Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease associates with platelet reactivity in humans. Here, using a human genomic proteomic approach, we identify high affinity, disease-relevant, potentially targetable interaction between SVEP1 the orphan receptor Platelet Endothelial Aggregation Receptor (PEAR1). This PEAR1 phosphorylation associated AKT/mTOR signaling cells...
Cardiac inflammation in heart failure is characterized by the presence of damage-associated molecular patterns, myeloid cells, and T cells. patterns provide continuous proinflammatory signals to cells through TLRs (toll-like receptors) that converge onto adaptor protein MyD88 (myeloid differentiation response 88). These induce activation into efficient antigen-presenting activate their TCR (T-cell receptor). T-cell results cardiotropism, cardiac fibroblast transformation, maladaptive...
BACKGROUND: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events patients with cancer, such as accelerated atherosclerosis. Of immune cells involved atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there no noninvasive approach to determine changes these vivo following ICI treatment and explore underlying mechanisms events. Herein, we aim use a CCR2 2)–targeted radiotracer...
Background Mixed valvular disease (MVD), mitral regurgitation (MR) from pre-existing in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated cardiac mortality. Despite prevalence MVD, quantitative understanding interplay between PVL, LV, and post-TAVR recovery meager. Methods Results We quantified effects MVD on valvular-ventricular hemodynamics using an...
<title>Abstract</title> Heart failure is caused in part by cardiac remodeling processes that include the death of myocytes and their replacement fibroblasts. We hypothesized these two cell types may harbor epigenetic contexts which heart disease-associated non-coding SNPs perturb gene expression relevant to disease. Accordingly, we generated high-resolution Hi-C data layered with functional genomic information annotate link putative distal regulatory elements loci promoters. Our analysis...
Regulatory T (Treg) cells have long been recognized as modulators of immunological tolerance and homeostasis. Previously, we used scRNA-seq to reveal significant Treg heterogeneity in response IL-2-induced activation. Herein, leveraged enrichment analyses, well bulk single nucleus multi-omics splenic lung Tregs, uncover confirm the importance transcription factors (TFs) chromatin remodeling Multiple bZIP TF motifs showed increased accessibility post IL-2 treatment, with correlated...
Vascular smooth muscle cell (VSMC) and immune diversification play a central role in driving atherosclerotic coronary artery disease (CAD). However, the molecular mechanisms governing state transitions within neo-intima human CAD remain poorly understood, no lipid-independent therapies are currently approved for its treatment. Here, we performed multi-omic single-cell gene expression profiling, epitope mapping, spatial transcriptomics from 27 arteries. Our analysis identified fibroblast...
Mechanisms that mediate allograft tolerance differ between organs. We have previously shown Foxp3+ T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and these cells suppress alloimmune responses locally systemically. Here, we demonstrated reside differed phenotypically transcriptionally from those the periphery were clonally expanded. Using a mouse re-transplant model, showed recipient continuously recruited to BALT within allografts....
<title>Abstract</title> CD14 is a widely validated marker for monocyte/macrophage activity as well an inflammatory biomarker and upstream regulator of macrophage activity. We herein test the hypothesis that interventional blockade with murine analogue atibuclimab, anti-CD14 antibody, which has recently been reported to have favorable safety profile, prevents secondary immunological exacerbation cardiac injury in translational mouse model reperfused ST-elevation myocardial infarction (STEMI)...