Date of Award
Doctor of Philosophy (PhD)
Cell & Molecular Biology
Mutations in CEP290 are associated with phenotypes ranging from early onset retinal degeneration to embryonic lethal, multisystem disease. The association of CEP290 with disease in multiple tissues is believed to be due to its role in stabilizing the primary cilium, an organelle found on almost every cell in the body whose involvement in human health and disease has only recently been identified. Like many ciliary proteins, CEP290’s exact function in this structure and how mutations affecting the protein lead to disease remains relatively unclear. Here, a proposed mechanism of CEP290-associated disease pathogenesis is explored, finding severity of CEP290-associated disease correlates with the amount of functional CEP290 protein predicted to result from a given patient’s genotype. In addition, a potential interaction between CEP290 and TTBK2, a kinase recently discovered to traffic to the base or the primary cilium before the onset of ciliogenesis, was observed, providing insight into a role of CEP290 in the early stages of cilium formation.
Wojno, Adam Paul, "Cep290 and the Primary Cilium- Understanding the Protein's Role in Ciliary Health and Disease" (2015). Publicly Accessible Penn Dissertations. 2098.