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Title page for ETD etd-11262012-232542

Type of Document Master's Thesis
Author Robinson, Jamille Yvette
Author's Email Address jamille.robinson@@vanderbilt.edu
URN etd-11262012-232542
Title The Role of Activin Receptor-like Kinases and Nuclear Factor κB in Type III Transforming Growth Factor β Receptor Signaling
Degree Master of Science
Department Interdisciplinary Studies: Cardiovascular Pharmacology
Advisory Committee
Advisor Name Title
Dr. Roger Chalkley Committee Chair
Dr. Charles Hong Committee Member
Dr. Joey V. Barnett Committee Member
  • transforming growth factor signaling
  • Type III TGF-beta receptor
  • Activin-receptor like kinases
  • NF-kappaB
  • valve development
Date of Defense 2012-11-15
Availability unrestricted
Congenital heart disease (CHD) is the most common type of birth defect affecting eight out of every 1,000 newborns, causing more deaths in the first year of life than any other birth defect. A significant fraction of CHD is associated with abnormal valve structure and function. A detailed understanding of the early signaling events that regulate and guide cardiac valve formation is required to identify new therapeutic targets. Here, I focus on the role of Type III Transforming Growth Factor β Receptor (TGFβR3) in Endocardial epithelial to mesenchymal transformation (EMT), a critical step in valvular development. Using an in vitro assay of endocardial EMT I used small molecule inhibitors to establish that ALK2 and ALK3 are both required for endocardial EMT. Specifically, I demonstrated that ALK2 and ALK3 are downstream of TGFβR3. Finally, I used small molecule inhibitors of the NF-κB pathway to implicate this signaling system in endocardial EMT. These studies identify and clarify the role of specific pathways endocardial EMT which furthers our understanding of TGFβR3 signaling and early valve formation.
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