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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11262012-232542 |
| Date | 07 December 2012 |
| Creators | Robinson, Jamille Yvette |
| Contributors | Dr. Roger Chalkley, Dr. Charles Hong, Dr. Joey V. Barnett |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11262012-232542/ |
| Rights | restrictsix, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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