Development of CRISPR-based mouse models for scalable and quantitative in vivo functional cancer genomics

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Abstract/Contents

Abstract
Large-scale genomic analyses of human cancers have catalogued somatic point mutations thought to initiate tumor development and sustain cancer growth. However, determining the functional significance of specific alterations remains a major bottleneck in our understanding of the genetic determinants of cancer. A diverse set of approaches—from genetic screens in cancer cell lines to the generation of defined alterations within organoids, allografts, and xenografts—have been used to study the function of genetic drivers of cancer. This thesis describes advances in cancer modeling that have stemmed from the implementation of genome-editing and next-generation sequencing in autochthonous mouse models of human cancer. Specifically, this dissertation focuses on the development and applications of higher-throughput mouse models that enable precise and quantitative analysis of the effects of multiplexed and/or combinatorial alterations on tumor growth in vivo. I discuss the potential impacts of these models on functional cancer genomics and outline the ways in which these models will improve our understanding of cancer. Finally, I speculate on additional innovations that will further increase the scope, precision, and value of in vivo models of human cancer.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2018; ©2018
Publication date 2018; 2018
Issuance monographic
Language English

Creators/Contributors

Author Winters, Ian Paul
Degree supervisor Winslow, Monte
Thesis advisor Winslow, Monte
Thesis advisor Fire, Andrew Zachary
Thesis advisor Lipsick, Joseph Steven, 1955-
Thesis advisor Sage, Julien
Degree committee member Fire, Andrew Zachary
Degree committee member Lipsick, Joseph Steven, 1955-
Degree committee member Sage, Julien
Associated with Stanford University, Department of Genetics.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Ian Paul Winters.
Note Submitted to the Department of Genetics.
Thesis Thesis Ph.D. Stanford University 2018.
Location electronic resource

Access conditions

Copyright
© 2018 by Ian Paul Winters
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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