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Full-Text Articles in Medicine and Health Sciences
A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose
A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …
Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu
Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu
Dissertations & Theses (Open Access)
High-throughput forward genetic screenings are invaluable tools to systematically explore genetic interactions and to link gene disruption with disease contexts. The adaptation of CRISPR/Cas9 has improved the sensitivity and specificity of functional screenings. Despite this advance, there remains a long-standing need to improve functional screenings with smaller and more versatile pooled libraries. Capitalizing on the inherent multiplexing capability of a class 2 CRISPR enzyme AsCpf1, we developed a multiplexed, high throughput screening strategy that has avoided the usual trade-off between library size and library penetration, allowing library minimization without sacrificing gene targeting efficiency. We optimized the AsCpf1 protein for functional …