- Congenital heart defects research
- Congenital Heart Disease Studies
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Tissue Engineering and Regenerative Medicine
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Cancer Immunotherapy and Biomarkers
- Cardiac Fibrosis and Remodeling
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Chemokine receptors and signaling
- Neuroscience and Neural Engineering
- Gene expression and cancer classification
- CAR-T cell therapy research
- Genetics and Physical Performance
- 3D Printing in Biomedical Research
- Gene Regulatory Network Analysis
- Cardiovascular Function and Risk Factors
- Metabolism, Diabetes, and Cancer
- interferon and immune responses
- Lipid metabolism and biosynthesis
Cardiovascular Institute of the South
2017-2024
Stanford University
2017-2024
Stanford Medicine
2020-2024
Institute for Stem Cell Biology and Regenerative Medicine
2023
California Institute for Regenerative Medicine
2019-2021
Pediatrics and Genetics
2019
Harvard University
2017-2018
Harvard Stem Cell Institute
2017-2018
Boston Children's Hospital
2017
Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing biology and enabling new insights into the physiology human organs. We created a reference atlas comprising nearly 500,000 cells from 24 different tissues organs, many same donor. This enabled molecular more than 400 types, their distribution across tissues, tissue-specific variation in gene expression. Using multiple single donor identification clonal T between mutation rate B cells,...
Background: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies used to activate the immune system against tumor cells. Despite therapeutic benefits, ICIs have potential cause immune-related adverse events such as myocarditis, a rare but serious side effect with up 50% mortality in affected patients. Histologically, patients ICI myocarditis lymphocytic infiltrates heart, implicating T cell–mediated mechanisms. However, precise pathological subsets and molecular changes unknown....
Abstract Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept identify cell types origin using the Tabula Sapiens transcriptomic atlas as well individual atlases in combination with Human Protein Atlas consensus dataset. define type signature scores, which allow inference that contribute cell-free for a variety diseases.
During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as first second heart fields, respectively. While these have been extensively studied in non-human model systems, their identification study vivo human tissues limited due to ethical technical limitations accessing gastrulation-stage embryos. Human-induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling embryogenesis well-established ability...
A major informatic challenge in single cell RNA-sequencing analysis is the precise annotation of datasets where cells exhibit complex multilayered identities or transitory states. Here, we present devCellPy a highly accurate and machine learning-enabled tool that enables automated prediction types across hierarchies. To demonstrate power devCellPy, construct murine cardiac developmental atlas from published encompassing 104,199 E6.5-E16.5 train to generate algorithm. Using this algorithm,...
Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within heart and indistinguishable from surrounding muscle tissue, is major complication in surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against CCS, allowing for visualization CCS vivo following single intravenous injection mice. These optical imaging tools showed high sensitivity, specificity, resolution, with no adverse effects on...
Abstract During normal lifespan, the mammalian heart undergoes limited renewal of cardiomyocytes. While exact mechanism for this remains unclear, two possibilities have been proposed: differentiated myocyte replication and progenitor/immature cell differentiation. This study aimed to characterize a population cardiomyocyte precursors in neonatal determine their requirement cardiac development. By tracking expression an embryonic Nkx2.5 enhancer, we identified cardiomyoblasts capable...
Abstract Generating cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) has represented a significant advance in our ability to model cardiac disease. Current differentiation protocols, however, have limited use due their production of heterogenous cell populations, primarily consisting ventricular-like CMs. Here we describe the creation two chamber-specific reporter hiPSC lines by site-directed genomic integration using CRISPR-Cas9 technology. In MYL2-tdTomato reporter,...
Abstract Density is a core material property and varies between different cell types, mainly based on differences in their lipid content. Sorting density enables various biomedical applications such as multi‐omics precision medicine regenerative repair medicine. However, significant challenge sorting cells of the same type differences. Here, new method for real‐time monitoring single inherent levitation profiles driven by content reported. As model system, human‐induced pluripotent stem...
The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change culture, often preserving some but not all their characteristics culture. At least the may be mimicked by providing specific cues cultured Here, we show that after isolation and during maintenance adherent rat islets reduce expression key β-cell transcription factors necessary for function soluble pancreatic decellularized matrix (DCM) can enhance gene...
Cardiomyocytes (CMs), the contractile heart cells that can be derived from human induced pluripotent stem (hiPSCs). These hiPSC CMs used for cardiovascular disease drug testing and regeneration therapies, they have therapeutic potential. Currently, hiPSC-CM differentiation cannot yet controlled to yield specific cell subtypes consistently. Designing processes consistently direct is important realize full potential of hiPSC-CMs. A model accurately represents dynamic changes in populations...
Summary Hypoplastic left heart syndrome (HLHS) is one of the most challenging forms congenital diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain abnormal development cardiac valve, septum, and vasculature, known to originate from endocardium. Here, using single-cell RNA profiling, induced pluripotent stem cells, human fetal tissue with an underdeveloped ventricle, we identified a developmentally impaired endocardial...
Hypoplastic left heart syndrome (HLHS) is one of the most challenging forms congenital diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain abnormal development cardiac valve, septum, and vasculature, known to originate from endocardium. Here, using single-cell transcriptomic profiling, induced pluripotent stem cells (iPSC) derived endocardial (iEECs), human fetal tissue with underdeveloped ventricle, as well a Xenopus...
ABSTRACT During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as first second heart fields, respectively. While these have been extensively studied in non-human model systems, their identification study vivo human tissues limited due to ethical technical limitations accessing gastrulation stage embryos. Human induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling embryogenesis well-established...