A5044623015- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Cardiac Fibrosis and Remodeling
- Cardiac Valve Diseases and Treatments
- Renal and related cancers
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Cardiac tumors and thrombi
- Silicon Carbide Semiconductor Technologies
- 3D Printing in Biomedical Research
- Cardiac Structural Anomalies and Repair
- Electrospun Nanofibers in Biomedical Applications
- RNA and protein synthesis mechanisms
- Protease and Inhibitor Mechanisms
University of Wisconsin–Madison
2017-2023
Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources into a wide range of chemicals. To broaden scope products beyond metabolites, methods enzymes accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries enzyme-coding sequences, but most biochemistries lack simple assay screen promising enzyme variants. Our solution this challenge is structure-guided mutagenesis in which...
Cardiomyocytes (CMs) generated from human pluripotent stem cells (hPSCs) are immature in their structure and function, limiting potential disease modeling, drug screening, cardiac cellular therapies. Prior studies have demonstrated that coculture of hPSC‐derived CMs with other cell types, including endothelial (ECs), can accelerate CM maturation. To address whether the differentiation stage at which ECs introduced affects maturation, authors progenitor (CPCs) analyze molecular functional...
Human pluripotent stem cell (hPSC)-derived cardiac therapies hold great promise for heart regeneration but face major translational barriers due to allogeneic immune rejection. Here, we engineered hypoimmunogenic hPSCs using a two-step CRISPR-Cas9 strategy: (1) B2M knockout, eliminating HLA class I surface expression, and (2) knock-in of HLA-E or HLA-G trimer constructs in the AAVS1 safe harbor locus confer robust evasion. Hypoimmunogenic maintained pluripotency, efficiently differentiated...
Human induced pluripotent stem cell derived cardiac fibroblasts (hiPSC-CFs) play a critical role in modeling human cardiovascular diseases
Introduction: Fibroblasts are mesenchymal cells that predominantly produce and maintain the extracellular matrix (ECM) critical mediators of injury response. In heart, valve interstitial (VICs) a population fibroblasts responsible for maintaining structure function heart valves. These regionally distinct from myocardial fibroblasts, including left ventricular cardiac (LVCFBs), which located in myocardium close vicinity to cardiomyocytes. Here, we hypothesize these subpopulations...
Cardiac fibroblasts (CFBs) support heart function by secreting extracellular matrix (ECM) and paracrine factors, respond to stress associated with injury disease, therefore are an increasingly important therapeutic target. We describe how developmental lineage of human pluripotent stem cell-derived CFBs, epicardial (EpiC-FB), second field (SHF-FB) impacts transcriptional functional properties. Both EpiC-FBs SHF-FBs exhibited CFB programs improved calcium handling in cardiac tissues....
Abstract Spatiotemporally controlled presentation of morphogens and elaborate modulation signaling pathways elicit pattern formation during development. Though this process is critical for proper organogenesis, unraveling the mechanisms developmental biology have been restricted by challenges associated with studying human embryos. Human pluripotent stem cells (hPSCs) used to model development in vitro, however difficulties precise spatiotemporal control cellular microenvironment limited...
Cardiac fibroblasts (CFBs) are a key therapeutic target due to their supportive roles during heart development and response injury disease. Here, we describe robust protocol differentiate human pluripotent stem cells (hPSCs) into CFBs through an epicardial intermediate. We discuss in detail the characterization of resulting epicardial-derived (EpiC-FBs) using immunofluorescence microscopy, flow cytometry, qPCR. anticipate that these EpiC-FBs can be applied drug testing, disease modeling,...