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Creators/Authors contains: "George, Olivia"

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  1. The First2 Network is an alliance of higher education institutions across the State of West Virginia striving to improve science, technology, engineering or math (STEM) education by supporting rural, first-generation, and underrepresented college students pursuing STEM majors.  Over the summers of 2019 and 2020, the First2 Network delivered two-week summer research immersion experiences at various institutions throughout West Virginia. The 2019 program was delivered on-campus at four universities while the 2020 program was delivered virtually, due to the COVID-19 pandemic, across nine sites. Before and after the immersion experience, students who participated in the program completed a variety of survey questionnaires for the assessment of their interests, expectations, identity and belonging in STEM. We found that the in-person experience in 2019 had better outcomes compared to the virtual experience, suggesting students conducting research directly under their faculty supervisors in-person and on-site will have a more positive impact on their STEM education and career. However, participation in the virtual format still resulted in an improvement in belonging and STEM identity, indicating that connecting with students remotely is still worthwhile when it is the most viable option. The student population in Appalachia faces a number of academic barriers, so there is much to gain by finding new ways to reach as many students as possible with early career development programs. 
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  2. Synthetic matrices with dynamic presentation of cell guidance cues are needed for the development of physiologically relevant in vitro tumor models. Towards the goal of mimicking prostate cancer progression and metastasis, we engineered a tunable hyaluronic acid-based hydrogel platform with protease degradable and cell adhesive properties employing bioorthogonal tetrazine ligation with strained alkenes. The synthetic matrix was first fabricated via a slow tetrazine-norbornene reaction, then temporally modified via a diffusion-controlled method using trans-cyclooctene, a fierce dienophile that reacts with tetrazine with an unusually fast rate. The encapsulated DU145 prostate cancer single cells spontaneously formed multicellular tumoroids after 7 days of culture. In situ modification of the synthetic matrix via covalent tagging of cell adhesive RGD peptide induced tumoroid decompaction and the development of cellular protrusions. RGD tagging did not compromise the overall cell viability, nor did it induce cell apoptosis. In response to increased matrix adhesiveness, DU145 cells dynamically loosen cell-cell adhesion and strengthen cell-matrix interactions to promote an invasive phenotype. Characterization of the 3D cultures by immunocytochemistry and gene expression analyses demonstrated that cells invaded into the matrix via a mesenchymal like migration, with upregulation of major mesenchymal markers, and down regulation of epithelial markers. The tumoroids formed cortactin positive invadopodia like structures, indicating active matrix remodeling. Overall, the engineered tumor model can be utilized to identify potential molecular targets and test pharmacological inhibitors, thereby accelerating the design of innovative strategies for cancer therapeutics. 
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