After 4 years as a Senior Research Specialist at the Vanderbilt Cell Imaging Resource (CISR) microscope facility, she joined the Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto. In addition to instruction, she has acted as the Associate Director, Undergraduate Programs at IBBME as well as the Associate Chair, Foundation Years in the Division of Engineering Science. Currently an Associate Professor, Teaching Stream, she serves as faculty supervisor for the Discovery program and is program co-director for the Igniting Youth Curiosity in STEM Program. Dawn was a 2017 Early Career Teaching Award recipient at U of T and was named the 2016 Wighton Fellow for excellence in development and teaching of laboratory-based courses in Canadian UG engineering programs.
High school science, technology, engineering, and math (STEM) curricula are generally knowledge-based in methodology and focus on content delivery in preparation for post-secondary study. However, the rapid technological change at the cutting edge and the rate of global integration in STEM highlight the importance in developing a holistic critical thinking framework for student learning. In 2016, graduate students at the Institute of Biomaterials & Biomedical Engineering created Discovery, a collaborative high school educational program focused on critical thinking skill development through inquiry in the context of biomedical engineering (BME) [1]. Aligning with demonstrated evidence that inquiry-based active learning approaches are more effective in enhancing student learning than traditional teaching methods [2], evaluation in Discovery reinforces the value of a differential learning environment for high school STEM students who struggle in a knowledge-focused classroom [3,4]. In addition, the Discovery model is shown to enhance student attitudes towards STEM and post-secondary education, meanwhile providing robust opportunity for graduate trainees to develop and apply pedagogical skills through development of curriculum appropriate for university-preparatory students. Program impact provides opportunities to discuss this unique learning framework, collaborative delivery strategy, and implementation strategy of Discovery as a resource for translation to disciplines beyond BME, and institutions beyond the University of Toronto.
BACKGROUND: Treatment of occluded vessels can involve angioplasty, stenting, and bypass grafting, which can be limited by restenosis and thrombosis. Drug-eluting stents attenuate restenosis, but the current drugs used are cytotoxic, causing smooth muscle cell (SMC) and endothelial cell (EC) death that may lead to late thrombosis. N-cadherin is a junctional protein expressed by SMCs, which promotes directional SMC migration contributing to restenosis. We propose that engaging N-cadherin with mimetic peptides can act as a cell type–selective therapeutic strategy to inhibit polarization and directional migration of SMCs without negatively impacting ECs. METHODS: We designed a novel N-cadherin–targeting chimeric peptide with a histidine-alanine-valine cadherin-binding motif, combined with a fibronectin-binding motif from Staphylococcus aureus . This peptide was tested in SMC and EC culture assays of migration, viability, and apoptosis. Rat carotid arteries were balloon injured and treated with the N-cadherin peptide. RESULTS: Treating scratch-wounded SMCs with the N-cadherin–targeting peptide inhibited migration and reduced polarization of wound-edge cells. The peptide colocalized with fibronectin. Importantly, EC junction, permeability, or migration was not impacted by peptide treatment in vitro. We also demonstrated that the chimeric peptide persisted for 24 hours after transient delivery in the balloon-injured rat carotid artery. Treatment with the N-cadherin–targeting chimeric peptide reduced intimal thickening in balloon-injured rat carotid arteries at 1 and 2 weeks after injury. Reendothelialization of injured vessels after 2 weeks was unimpaired by peptide treatment. CONCLUSIONS: These studies show that an N-cadherin–binding and fibronectin-binding chimeric peptide is effective in inhibiting SMC migration in vitro and in vivo and limiting neointimal hyperplasia after balloon angioplasty without affecting EC repair. These results establish the potential of an advantageous SMC-selective strategy for antirestenosis therapy.
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