A5068603192- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Neuroscience and Neural Engineering
- CRISPR and Genetic Engineering
- Cerebral Palsy and Movement Disorders
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Stroke Rehabilitation and Recovery
- Botulinum Toxin and Related Neurological Disorders
- Mitochondrial Function and Pathology
- Cardiovascular Function and Risk Factors
- Elasticity and Material Modeling
- Trypanosoma species research and implications
- Additive Manufacturing and 3D Printing Technologies
- Muscle Physiology and Disorders
- Cellular transport and secretion
- Genetics, Aging, and Longevity in Model Organisms
- Cardiac Fibrosis and Remodeling
- Cardiac Valve Diseases and Treatments
Boston University
2019-2024
Harvard University
2021-2024
Polytechnic University of Puerto Rico
2024
United States Food and Drug Administration
2024
Johns Hopkins University
2016-2019
Shirley Ryan AbilityLab
2016
Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption the heart patient risks for arrhythmias failure. Recent studies show missense myosin, molecular motor of sarcomere, are clustered residues participate dynamic conformational states proteins. We hypothesized these conformations essential to adapt contractile output conservation pathophysiology HCM results from...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature nonlinear hiPSC-CMs, which technically challenge accurate functional interrogation contractile parameters beating cells. Furthermore, existing analysis methods relatively low-throughput, indirectly assess contractility, or...
SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments establishes replication are poorly defined. Here, we generated a panel phenotypically diverse, SARS-CoV-2-infectible human cell lines representing different body organs performed longitudinal survey proteins pathways broadly affected by virus. This revealed universal inhibition interferon signaling across...
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Hypertrophic cardiomyopathy is one of the most common inherited cardiomyopathies and a leading cause sudden cardiac death in young adults. Despite profound insights into genetics, there imperfect correlation between mutation clinical prognosis, suggesting complex molecular cascades driving pathogenesis. To investigate this, we performed an integrated quantitative multi-omics (proteomic, phosphoproteomic, metabolomic) analysis to illuminate early direct consequences mutations myosin heavy...
Using two-photon direct laser writing, we developed a versatile platform to generate, scale, and study hiPSC-derived engineered heart tissues (EHTs) in various geometries, with the goal of promoting fiber alignment maturation EHTs.
To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients predominantly Chinese ancestry.We sequenced HCM disease genes Singaporean (n=224) and controls (n=3634), compared findings with additional populations White cohorts (n=6179), performed vitro functional studies.Singaporean had significantly fewer confidently interpreted variants (pathogenic/likely pathogenic: 18%, P<0.0001) but an excess uncertain significance (24%, P<0.0001), as to Whites 31%, significance:...
PKP 2 mutations lead to instability in cell-cell junctions and sarcomeres that impairs cardiac tissue contractility ACM.
Highlights•Decellularized myocardial slices were repopulated with hiPSC-CMs to make EHS•EHS exhibited coordinated contractions and anisotropic electrical conduction•EHS cultured retained contractile function for >200 days•EHS had different sensitivities ion channel drugs than cell monolayersSummaryHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise cardiac studies, but their structural functional immaturity precludes use as faithful models of adult...
Heterozygous truncating variants in the sarcomere protein titin (TTN) are most common genetic cause of heart failure. To understand mechanisms that regulate abundant cardiomyocyte TTN expression we characterized highly conserved intron 1 sequences exhibited dynamic changes chromatin accessibility during differentiation human cardiomyocytes from induced pluripotent stem cells (hiPSC-CMs). Homozygous deletion these mice caused embryonic lethality while heterozygous demonstrated allele-specific...
Abstract SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments establishes replication are poorly defined. Here, we performed global proteomic analysis virus-host interface in a newly established panel phenotypically diverse, SARS-CoV-2-infectable human cell lines representing different body organs. This revealed universal inhibition interferon signaling across...
Abstract Introduction Cardiac contractility modulation (CCM) is a medical device‐based therapy delivering non‐excitatory electrical stimulations to the heart enhance cardiac function in failure (HF) patients. The lack of human vitro tools assess CCM hinders our understanding mechanisms action. Here, we introduce novel chronic (i.e., 2‐day) assay evaluate effects 3D microphysiological system consisting engineered tissues (ECTs). Methods Cryopreserved induced pluripotent stem cell‐derived...
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the left ventricular wall, diastolic dysfunction, and fibrosis, associated with mutations in genes encoding sarcomere proteins. While vitro studies have used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study HCM, these models not examined multicellular interactions involved fibrosis. Using engineered cardiac microtissues (CMTs) composed HCM-causing MYH7 -variant hiPSC-CMs wild-type fibroblasts,...
The Modified Ashworth Scale (MAS) is an assessment that often used by clinicians to grade spasticity in the affected limbs of stroke survivors. MAS a function angle at which clinician perceives resistance stretch and/or `catch' during passive joint rotation. qualitative nature combination with low resolution scale could result varied grouping spastic patients, even for single score. objective this pilot study was develop method quantification MAS, provide greater and eventually guide better...
Abstract The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured examined exhibit...
Abstract Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, designing therapies. Here we use a method not commonly applied biological materials, small angle x-ray scattering, characterize hiPSC-CMs within three-dimensional engineered tissues during their preliminary stages maturation. An scattering experimental...
Movies of human induced pluripotent stem cell (hiPSC)-derived engineered cardiac tissue (microbundles) contain abundant information about structural and functional maturity. However, extracting these data in a reproducible high-throughput manner remains major challenge. Furthermore, it is not straightforward to make direct quantitative comparisons across the multiple
Movies of human induced pluripotent stem cell (hiPSC)-derived engineered cardiac tissue (microbundles) contain abundant information about structural and functional maturity. However, extracting these data in a reproducible high-throughput manner remains major challenge. Furthermore, it is not straightforward to make direct quantitative comparisons across the multiple vitro experimental platforms employed fabricate tissues. Here, we present "MicroBundlePillarTrack," an open-source optical...
Background: Heterozygous truncating variants in the sarcomere protein titin (TTN) are most common genetic cause of heart failure, a major morbidity and mortality. This causality indicates that even two-fold changes amount TTN can profoundly disturb cardiac physiology. Although critical role formation cardiomyocyte contractility is well established, mechanisms regulating transcription gene remain poorly understood. Methods: We performed bioinformatics analysis to identify putative...
Abstract Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, designing therapies. Here, we used a method not commonly applied biological materials, small angle X-ray scattering characterize human induced within 3D engineered tissues during their preliminary stages maturation. An innovative experimental setup enabled visualization...
Understanding the structural and functional development of human-induced pluripotent stem-cell-derived cardiomyocytes is essential to engineering cardiac tissue that enables pharmaceutical testing, modeling diseases, designing therapies. Here we use a method not commonly applied biological materials, small angle X-ray scattering, characterize within 3D engineered tissues during their preliminary stages maturation. An scattering experimental reliable characterization cardiomyocyte myofilament...