Publication Date

2016-03-17

Availability

Embargoed

Embargo Period

2018-03-17

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Molecular and Cellular Pharmacology (Medicine)

Date of Defense

2016-01-13

First Committee Member

Claes Wahlestedt

Second Committee Member

Miguel Perez-Pinzon

Third Committee Member

Kerry Burnstein

Fourth Committee Member

Grace Zhai

Fifth Committee Member

Shaun Brothers

Abstract

Glioblastoma Multiforme is a malignant grade IV glioma that is responsible for 3-4% of all cancer related deaths. Unlike other glioma subtypes, glioblastoma multiforme has a poor median survival of 12.6 months due to unique treatment limitations highlighting the necessity of new therapeutics. A novel mechanism of HIF-2α in which the protein mediates hypoxia specific translation has been discovered. This research project suggests that hypoxia specific translation is uncoupled from the hypoxia specific transcription that HIF-2α historically participates. Furthermore, this project proposes the identification of HIF-2α translation specific structure requirements as a basis for future therapeutic target analysis. Evidence that HIF-2α and RBM4 act as direct binding partners in this hypoxic translation pathway was revealed and may provide an avenue for small molecule development to block their interaction. Modification of the hypoxic translation pathway through epigenetic regulation was similarly proposed in conjunction with the development of a high-throughput assay to measure change in the rate of translation.

Keywords

GBM; HIF-2α; RBM4; Alphascreen; Puromycin

Available for download on Saturday, March 17, 2018

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