Role of Primary Cilium-Mediated Signaling in Development, Disease and Cancer

Date

2018-07-27

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Abstract

The primary cilium serves as an antenna in most vertebrate cells. Dysfunction of the primary cilium is associated with a variety of diseases, called "ciliopathies". Mechanisms underlying ciliogenesis have been well studied. However, deciphering the role of cilia in cellular signaling pathways is critical in understanding the basis behind the varied ciliopathic phenotypes, and remains a frontier mostly unexplored. Primary cilia are required for vertebrate Shh signaling. The final output of the Shh pathway is the formation of Gli transcriptional activators or repressors, both of which occur in a cilia-dependent manner. However, the role of cilia-generated signaling during development, particularly that of the poorly understood negative regulation and basal suppression of sonic hedgehog (Shh) signaling and its relationship to hyperproliferative conditions such as cystic kidney disease and carcinogenesis is not well understood. Here, I studied the role of primary cilium-generated signaling in the context of development and disease. Particularly, I focused on the role of poorly understood negative regulation of Shh signaling and ciliary trafficking in the context of cellular signaling pathways. My studies provide key insights into the role of: (a) novel mechanisms for trafficking adenylyl cyclases to cilia in Shh signaling during neural tube development; (b) primary cilium-generated signaling in cystic kidney disease; (c) and role of basal suppression of Shh pathway and cilia in Shh-subtype medulloblastoma initiation, progression and prognosis. In addition, I contributed to other projects on the role of negative regulation of Shh signaling in limb and skeletal development, and regulation of ciliary trafficking of membrane proteins. Overall, my projects highlight the importance of cilium-generated signaling, particularly that of negative regulation of Shh signaling in embryonic development, cystic kidney disease, and Shh-subtype medulloblastoma.

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The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.

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Subjects

Cilia, Intracellular Signaling Peptides and Proteins, Kidney Diseases, Cystic, Medulloblastoma, Receptors, G-Protein-Coupled, Signal Transduction

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