Graduation Date

Fall 12-15-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Ali Nawshad

Abstract

The transforming growth factor (TGF) – β signaling pathway regulates a diversity of fundamental cellular processes such as cell growth and proliferation, cell differentiation, migration, apoptosis and other biological functions, both during embryogenesis and in adult tissue homeostasis. TGF-β is known to play a critical role in palatal development as in TGF-β knockout murine models, TGF-β deficiency causes cleft palate, a common craniofacial deformity in humans due to the abnormality of growth, elevation or fusion of the two palatal shelves. In order to investigate the mechanisms of how TGF-β regulates palatogenesis, we generated TGF-β3 knockout (-/-) murine models, performed systematic analysis of the transcriptomes of palatal tissue and identified dysregulated genes which are potentially responsible for occurrence of cleft palate. Moreover, we demonstrated that recombinant EphB2/Fc treatment-induced activation of ephrin reverse signaling was sufficient to rescue palatal fusion when TGF-β3 signaling was blocked. In addition, in oral squamous cell carcinoma, we revealed that TGF-β1 increased OSCC cell proliferation by upregulating the expression of ΔNp63 and c-Myc oncogenes and therefore promoted cancer progression. Furthermore, we established standard experimental periodontitis models in rats and by taking advantage of RNA-Seq technology, we successfully revealed that mechanisms of Simvastatin-induced periodontal bone regeneration. These data highlight the pivotal role of TGF-β signaling in craniofacial development, malignancies, and tissue regeneration.

Available for download on Saturday, December 08, 2018

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