Drosophila Glioblastoma Model to Study Signaling Pathways

Date of Award

5-5-2024

Degree Name

M.S. in Biology

Department

Department of Biology

Advisor/Chair

Madhuri Kango-Singh

Abstract

Objective: Glioblastoma (GBM) is a highly aggressive and malignant brain tumor that has limited treatment options and has an extremely poor prognosis (Waghmare et al. 2014). The amplification of Epidermal Growth Factor Receptor- VIII (EGFR-VIII) and activation of the Phosphatidyl Inositol 3-Kinase (PI3K) pathway are common genetic alterations observed in GBM patients (An et al. 2018). Our objective is to model GBM in Drosophila melanogaster and study the signaling pathways that promote GBM growth and inhibit cell death. Specifically, we aim to investigate the roles of MAPK, Hippo, and WNT signaling pathways in regulating GBM growth and Cactus expression, which regulates the JNK pathway. Methods: Our project involves genetic crosses that produce larvae with GBM, followed by brain dissections and immunohistochemistry to study changes in signaling pathways that promote GBM growth. Specifically, we are studying the early time points to understand the roles of signaling pathways like MAPK, Hippo, and WNT in promoting GBM growth and/or inhibiting cell death. By comparing our GBM models to experimental controls, we aim to generate initial data for designing further genetic experiments to identify specific signaling interactions that affect cell death and proliferation. We will use two lines, (1) y w UAS PI3K92E; +; Repo-Gal4 and (2) UAS GFP/TM3B,Sb, and (2) y w; UAS EGFRλtop/TM6C, to generate glioma in Drosophila, and investigate whether the Hippo pathway regulates Cactus, which also regulates the JNK pathway. Significance: The proposed research has significant implications for understanding the molecular mechanisms underlying GBM growth and identifying key molecules and pathways that drive this deadly disease. Using Drosophila as a model system allows for efficient genetic manipulation and provides a cost-effective way to study complex biological processes. Additionally, the results of this study will contribute to our understanding of GBM.

Keywords

Drosophila, Glioblastoma, GBM, Immunohistochemistry, JNK, DIAP1, MMP1, Hippo Pathway, WNT

Rights Statement

Copyright 2024, author

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