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Budding yeast discovery tools for neurofibromatosis type 1.

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Author	Wood, Matthew Duncan
Title	Budding yeast discovery tools for neurofibromatosis type 1.
Date	2010
Abstract	Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes affected individuals to a variety of benign and malignant nervous system tumors. NF1 is caused by a mutation in the NF1 tumor suppressor gene, which encodes neurofibromin, a negative regulator of the Ras signaling pathway. Approximately 10% of NF1 patients will suffer from malignant peripheral nerve sheath tumor (MPNST), a life-threatening condition. MPNST responds poorly to standard chemotherapeutics, and surgical resection is often impossible due to the intimate association with nerve structures. Despite 20 years of knowing the molecular defect responsible for NF1, no effective targeted therapeutic approaches for MPNST yet exist. In addition, the factors that drive MPNST development in NF1 individuals are incompletely understood. The NF1 gene is conserved in the budding yeast Saccharomyces cerevisiae, a tractable model organism for both chemical and genetic screens. The aim of the present work is to use the yeast system to identify small molecules that could be developed to treat NF1-associated MPNST, and to develop approaches to identify the pathways targeted by these molecules. A second aim is to use the yeast system to determine how NF1 loss alters the cellular response to DNA damage, an important driver of malignant progression. This work provides insight into novel therapeutic pathways to target MPNST, and provides a large set of small molecules for new investigations and possible development as anticancer agents.
Description	1 online resource (xi, 175 leaves) : illustrations (some color)
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D)--Dartmouth College.
Copyright	In Copyright. This material is protected by copyright and/or related rights. You are free to use this material in any way that is permitted by copyright law that applies to your use. For other uses, you need to obtain permission from the rights-holder(s). http://rightsstatements.org/page/InC/1.0/
DOI	https://doi.org/10.1349/ddlp.3495

Title	wood2010 1
Full Text	Budding Yeast Discovery Tools for Neurofibromatosis Type 1 A Thesis Submitted to the faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pharmacology and Toxicology by Matthew Duncan Wood DARTMOUTH COLLEGE Hanover, NH June 7, 2010

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Budding yeast discovery tools for neurofibromatosis type 1.

Budding yeast discovery tools for neurofibromatosis type 1.