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Title page for ETD etd-07192013-104828


Type of Document Dissertation
Author Tanksley, Jarred Paul
URN etd-07192013-104828
Title Tales of three signaling pathways: EGFR, TGFB, and WNT signaling in the GI tract
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
David Bader Committee Chair
Christopher Wright Committee Member
Kay Washington Committee Member
Mark deCaestecker Committee Member
Keywords
  • NEDD4
  • ubiquitin
  • EGFR
  • TGF-beta
  • WNT
  • Menetriers disease
  • Juvenile Polyposis
  • Colorectal cancer
Date of Defense 2013-07-09
Availability unrestricted
Abstract
My study of three signaling pathways in the context of three gastrointestinal diseases is presented here. Firstly, the epidermal growth factor receptor (EGFR) pathway and its role in the pathogenesis of the hypertrophic gastropathy Ménétrier's disease will be introduced. I will discuss the results of a clinical trial demonstrating that cetuximab, an EGFR pathway inhibitor, is the first effective medical therapy against Ménétrier's disease. I will then introduce the transforming growth factor-β (TGFB) pathway, and its role in the disorder juvenile polyposis syndrome (JPS). I will compare the clinico-pathological presentation of JPS to that of Ménétrier's disease, and suggest that there is a role for aberrant EGFR signaling in the pathogenesis of JPS. Finally, I will discuss my studies of the canonical WNT signaling pathway in the context of colorectal cancer (CRC). This part of the dissertation will center on my findings that the E3 ubiquitin ligase, NEDD4L, is a canonical WNT pathway inhibitor that is downregulated early in CRC, and may serve a tumor-suppressive role in CRC.
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