Author ORCID Identifier

orcid.org/0000-0001-7148-2789

Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Dr. Xiang-Yang (Shawn) Wang

Abstract

Abstract

THE CHARACTERIZATION OF CHIMERIC CHAPERONE FLAGRP170 AS A NOVEL RADIOPROTECTANT

By Tyler Nguyen, M.S.

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2017

Major Director: Dr. Xiang-Yang (Shawn) Wang, Ph.D., Professor, Department of Human and Molecular Genetics

Radiation therapy (RT) is restricted by toxic effects on adjacent normal tissue, which limits RT efficacy in cancer treatment. Damage to normal tissue, such as radiosensitive intestine and bone marrow compartments, results in acute radiation damage. To reduce normal tissue injury in the setting of RT, we examine the potential radioprotectant, Flagrp170, a chimeric protein. Flagrp170 is comprised of glucose-regulated protein-170 (Grp170) and a NF-κB activating sequence derived from flagellin. We show that Flagrp170 can protect normal tissues post irradiation, indicated by TUNEL and clonogenic assays. However, treatment with Flagrp170 does not influence tumor response to RT. Studies indicate that Flagrp170 activates the transcription factor NF-κB, a strong pro-survival signal. In addition, Flagrp170 can induce production of radioprotective cytokines as well. Data suggests that Flagrp170 has potential as a novel radioprotectant in the setting of RT. The combination of Flagrp170 therapy and RT may lead to improved treatment outcomes.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-10-2017

Available for download on Friday, August 10, 2018

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