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The Role of Cell-polarity in Development and Disease

From the simplest unicellular organisms to complex metazoans, cell polarity is a widespread characteristic that is essential for almost every aspect of biology. Proper polarization of cells is crucial for the establishment and maintenance of higher order structures such as tissue and organs. Cell polarity refers to the asymmetric distribution of various macromolecules and cellular structures, resulting in polarized architecture and function of the cell. Defects in cell polarity lead to various phenotypes, ranging from aberrant signaling, proliferation, cell adhesion and migration, cell fate determination and pluripotency, as well as embryonic lethality, neoplasia and cancer. Given the various roles for cell polarity in development and disease, the characterization of the components involved in polarity and their mechanisms of function is of great importance.
My thesis work has encompassed three major projects, each of which is focused on understanding the role of cell polarity in development and disease. Although genetic screens in invertebrates have led to the identification of a number of cell-polarity proteins, similar systematic approach have not been undertaken in mammalian systems. The goal of my first project was to design and implement a high-throughput screen to systematically knockdown individual genes using siRNA, and then assess cell junction integrity as a measure of cell polarity. Given the importance of cell polarity to signaling pathways, I next sought to determine the mechanism by which cell polarity affects TGFβ and Hippo pathways, two important signaling pathways involved in development and disease. Lastly, by studying the acquisition of pluripotency by somatic cells, I uncovered a central role for cell polarity in the establishment and maintenance of pluripotency. Here I will present and discuss our discovery pertaining to the role of cell polarity in cell signaling and pluripotency.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43734
Date14 January 2014
CreatorsSamavarchi-Tehrani, Payman
ContributorsWrana, Jeffrey
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis, Dataset

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