Kaitlin Fisher

Graduate Student

email: kfisher (at) ucsd.edu


Research Description

IL-33 (an Interleukin-1 family member) has been identified as a key participant in immune and inflammatory responses. However, the structural homology between IL33 and other members of the interleukin family are low- presenting unique sequence identity, unique receptor interactions, and potentially unique signaling mechanisms associated with its activity. The current, limited understanding of IL-33 is that it functions as an extracellular signaling factor.  However, IL33 lacks a typical N-terminal signaling sequence for transport through the ER and Golgi Apparatus.  This lack of a signaling sequence categorizes IL33 as a non-classically secreted protein, the mode of which is currently under investigation.  We believe that Interleukin-33 is able to interact with lipid bi-layers as part of its secretory pathway. Previous work done on similar beta-trefoil motif proteins with non-classical secretion pathways (IL-1β) shows that there is indeed a membrane interaction with a significant portion of the trefoil structure.  Additionally, work on other interleukins (IL-32) show membrane localization upon stimulation in epithelial cells. Given interleukin-33’s role in heart protection, I want to understand more fully the influence that structure has on its ability to signal effectively and how this signaling is facilitated by effective transport from the cell.  In addition, I am looking at the structural details of IL33 and other interleukin family members to better understand not only their secretion, but activity within the cell.