A5087720075- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
- Integrated Circuits and Semiconductor Failure Analysis
- Tissue Engineering and Regenerative Medicine
- Histone Deacetylase Inhibitors Research
- 3D Printing in Biomedical Research
- Electrochemical Analysis and Applications
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Cardiac pacing and defibrillation studies
- Nuclear Structure and Function
- Heart Failure Treatment and Management
- Ion channel regulation and function
- Viral Infectious Diseases and Gene Expression in Insects
University of Michigan
2017-2024
Michigan Medicine
2020-2023
Core Laboratories (United States)
2019-2021
Abstract The immature phenotype of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a major limitation to the use these valuable cells for pre-clinical toxicity testing and disease modeling. Here we tested hypothesis that perinatal extracellular matrix (ECM) promotes hiPSC-CM maturation greater extent than mouse ECM. We refer ECM as Matrix Plus (Matrix Plus) compare effects commercially available (Matrigel). hiPSC-CMs cultured on mature functionally structurally...
Abstract We validated 3 distinct hiPSC-CM cell lines—each of different purity and a voltage sensitive dye (VSD)-based high-throughput proarrhythmia screening assay as noncore site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate, or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison, Wisconsin, iCell...
Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) have been used extensively to model inherited heart diseases, but hiPSC-CM models of ischemic disease are lacking. Here, our objective was generate an disease. To this end, hiPSCs were differentiated into functional hiPSC-CMs and then purified using either a simulated ischemia media or by magnetic antibody-based purification targeting the nonmyocyte population for depletion from cell population. Flow cytometry analysis...
hiPSC-CMs are being considered by the Food and Drug Administration other regulatory agencies for in vitro cardiotoxicity screening to provide human-relevant safety data. Widespread adoption of academic science is limited immature, fetal-like phenotype cells. Here, advance maturation state hiPSC-CMs, we developed validated a human perinatal stem cell-derived extracellular matrix coating applied high-throughput cell culture plates. We also present validate cardiac optical mapping device...
Membrane proteins constitute a substantial fraction of the human proteome, thus representing vast source therapeutic drug targets. Indeed, newly devised technologies now allow targeting "undruggable" regions membrane to modulate protein function in cell. Despite advances technology, rapid translation basic science discoveries into potential candidates transmembrane domains remains challenging. We address this issue by harmonizing single molecule-based and ensemble-based atomistic simulations...
A common genetic risk factor for bipolar disorder is the CACNA1C gene, a gene also critical cardiac rhythm. The impact of mutations on patient rhythm unknown. Here we report electrophysiological implications associated in using induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Results indicate related mutation causes electrical impulse conduction slowing mediated by impaired intercellular coupling via connexin43 gap junctions. In vitro therapy to restore expression increased...
Human induced stem cell-derived cardiomyocytes (hiPSC-CMs) are used to replace and reduce the dependence on animals animal cells for preclinical cardiotoxicity testing. In two-dimensional monolayer formats, hiPSC-CMs recapitulate structure function of adult human heart muscle when cultured an optimal extracellular matrix (ECM). A perinatal ECM (maturation-inducing matrix-MECM) matures hiPSC-CM structure, function, metabolic state in 7 days after plating. Mature monolayers also respond as...
Background: Epigenetic histone acetylation is a major event controlling cell functions, such as metabolism, differentiation and repair. Here, we aim to determine whether Valproic acid (VPA), FDA approved inhibitor of deacetylation for bipolar disease, could protect heart against myocardial infarction (MI) injury elucidate key molecular pathways. Methods: VPA was administrated MI rats at different time points, onset after injury. Echocardiography, histology, serum biology assays, gene...
Abstract Membrane proteins constitute a substantial fraction of the human proteome, thus representing vast source therapeutic drug targets. Indeed, newly devised technologies now allow targeting “undruggable” regions membrane to modulate protein function in cell. Despite advances technology, rapid translation basic science discoveries into potential candidates transmembrane domains remains challenging. We address this issue by harmonizing single molecule-based and ensemble-based atomistic...
Human induced stem cell-derived cardiomyocytes (hiPSC-CMs) are used to replace and reduce the dependence on animals animal cells for preclinical cardiotoxicity testing. In two-dimensional monolayer formats, hiPSC-CMs recapitulate structure function of adult human heart muscle when cultured an optimal extracellular matrix (ECM). A perinatal ECM (maturation-inducing matrix-MECM) matures hiPSC-CM structure, function, metabolic state in 7 days after plating. Mature monolayers also respond as...