Browsing by Subject "beta-catenin"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Drug development and novel combination strategies with phytochemicals for precision medicine in cancer
    (2017-08) Shin, Seung Ho
    Precision medicine refers to matching the most accurate and effective treatment to each individual, and has the potential to manage diseases. In cancer, however, developing drug candidates and finding effective combination strategies are in great demand. Here, we present a framework covering drug development against a specific oncoprotein, effective combinations of drug and natural compounds, and a physiologically-achievable chemoprevention strategy. First, HI-B1 is synthesized and identified as a direct β-catenin inhibitor. A colon cancer patient-derived xenograft (PDX) model with a high level of β-catenin is sensitive to HI-B1. Second, a combination of aspirin with a ginger extract shows synergistic effect. Combining a ginger extract with aspirin treatment can significantly reduce the effective dose of aspirin while retaining its therapeutic effects in PDX mouse models. Third, multiple phytochemicals at low doses accumulatively inhibit one key protein to exert their chemopreventive and therapeutic effects. Natural ERK2 inhibitors are discovered using chemoinformatics, crystallography, cell biology and biochemistry. Each outcome could be used in a precision oncology workflow to help prevent and treat cancer efficiently.
  • Thumbnail Image
    Item
    Extracellular Matrix Guided Endothelial Differentiation
    (2022-08) Hall, Mikayla
    Cardiovascular disease is the leading cause of death worldwide. Due to recent advances including development of induced pluripotent stem cells, cardiac tissue engineering has emerged as a promising avenue for in vitro drug and device testing as well as eventual transplantation. Nutrient flow presents one of the major challenges to large scale engineered cardiac tissues which is necessary for many of the potential applications of engineered tissues. The lack of nutrient flow could be solved through tissue vascularization which requires endothelial cells lining vessels. The extracellular matrix (ECM) plays a vital role in tissue development and the majority of in vitro differentiation protocols rely on ECM substrates. Here we present two studies which investigate the role of the ECM in endothelial differentiation and the mechanisms activated by ECM engagement during differentiation. First, we investigate the role of individual ECM proteins in endothelial differentiation and elucidate pathways key to how ECM interactions promote differentiation. Second, a Design of Experiments approach was utilized to optimize the ECM composition for endothelial differentiation. The foundation of this work is a thorough knowledge of the role of the ECM during development, which guides protein selection and mechanistic investigation. An improved understanding of the role of ECM during in vitro differentiation will lead to better differentiation protocols and the potential for in situ differentiation. Ultimately, these studies will inform methods for engineered tissue vascularization to improve cell survival in large scale engineered tissues.