Date of Award

Summer 6-29-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

First Advisor

Prof. Surya Nauli

Second Advisor

Dr. Ajay Sharma

Third Advisor

Dr. Aftab Ahmed

Fourth Advisor

Dr. Moom Roosan

Abstract

Primary cilia are sensory organelles present in most mammalian cell types and regulate cell cycle and signaling pathways. Biochemical and molecular dysfunctions of primary cilia are associated with a wide range of diseases, including cancer, ciliopathies polycystic kidney disease (PKD, liver disorders, mental retardation, and obesity to cardiovascular diseases. Dysfunction in endothelial cilia contributes to aberrant fluid-sensing and results in vascular disorders, such as hypertension, aneurysm, and atherosclerosis. In this dissertation, the most recent outcomes on the roles of endothelial primary cilia within vascular biology have been summarized. Moreover, we evaluate the correlation between cilia formation or length and cell cycle or division using PKD and cancer epithelia. The results show that these cells were associated with abnormal ploidy and were highly proliferative compared with normal kidney epithelia (NK). Importantly, the cancer epithelial cells show a reduction in the presence and/or length of primary cilia. Restoration of the expression and length of primary cilia in these cells using rapamycin were inversely correlated with cell proliferation. Our data suggest that primary cilia may serve as a novel target in cardiovascular disorder and cancer.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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