Thompson, Elizabeth2021-02-222021-02-222020-12https://hdl.handle.net/11299/218676University of Minnesota M.S. thesis. December 2020. Major: Clinical Research. Advisor: Logan Spector. 1 computer file (PDF); vi, 72 pages.Background: Dystrophic epidermolysis bullosa (DEB) is a skin blistering disease caused by mutations in the COL7A1 gene, which encodes type VII collagen (C7). There is potential therapeutic benefit for DEB patients in identifying compounds that can increase C7 production in skin. Methods: A keratinocyte C7 reporter cell line was created and used in a genome-wide CRISPR activation (CRISPRa) screen to identify genes and pathways that increase C7 expression. Based on the CRISPRa screen results, a targeted drug screen was performed in three different keratinocyte cell lines to evaluate C7 upregulation. Results and Conclusions: The C7_tdTomato cell line was validated as an effective C7 reporter cell line. The CRISPRa screen identified two genes, DENND4B and TYROBP as top hits and pathway analysis showed enrichment of immune signaling pathways and regulators. The targeted drug screen identified kaempferol as a potential precision medicine for DEB.enThesis or Dissertation