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Electronic Thesis and Dissertation Repository

2016

Efferocytosis

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Evaluation Of Mertk Evolution And Efferocytosis Signalling, Amanda L. Evans Aug 2016

Evaluation Of Mertk Evolution And Efferocytosis Signalling, Amanda L. Evans

Electronic Thesis and Dissertation Repository

The TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases allow phagocytes to engage in the phagocytic removal of apoptotic cells. Although all three members of the TAM family are structurally homologous and function in a similar fashion, both human genome-wide association studies and knockout mice models have demonstrated that MERTK is the critical member of the TAM family for maintaining homeostasis. In this thesis, an evolutionary analysis was used to provide insight into the function of MERTK. Selection analysis in primates unexpectedly revealed a high degree of recent positive selection in MERTK’s signal peptide and transmembrane domain, …


Evolutionary History And Biological Regulation Of Cd93, Jack W D Blackburn Aug 2016

Evolutionary History And Biological Regulation Of Cd93, Jack W D Blackburn

Electronic Thesis and Dissertation Repository

CD93 is a transmembrane C-type lectin expressed on myeloid, endothelial, and B cells. First identified as a developmental B cell marker and a phagocytic C1q receptor, little is known about the role and mechanism of CD93 in efferocytosis (the phagocytosis of apoptotic cells). CD93 knockout mice develop chronic inflammatory diseases characterized by a lack of efferocytosis such as atherosclerosis and a lupus-like autoimmune disease. In humans, a cleaved form of CD93 (sCD93) is elevated during inflammation and autoimmune responses, and CD93 polymorphisms are associated with enhanced susceptibility to atherosclerosis and lupus. Despite these clinical associations, no comprehensive bioinformatic analysis of …