Neal Iwakoshi, PhD
Department of Surgery
Emory University School of Medicine
The unfolded protein response (UPR) is a signaling pathway that is activated when unfolded proteins accumulate in the endoplasmic reticulum (ER). Signals emanating from the ER induce a transcriptional program that enables a cell to survive conditions during which protein folding in the ER is compromised. Our lab is interested in the molecular basis of this highly coordinated response that it is essential for the folding, processing, export and degradation of all proteins emanating from the ER during stressed and normal conditions. The UPR exists in all eukaryotes and consists of multiple signaling pathways.
Current projects in the lab are focused on the most conserved of these pathways that involves a transmembrane kinase and endoribonuclease called IRE-1 and its transcriptional activator XBP-1. We employ biochemical and genetic tools to study the mechanisms that regulate the UPR within the immune system. To date the most physiologically relevant system to study the UPR has been the highly secretory immunoglobulin secreting plasma cell. Our studies within the plasma cell have led us to explore molecular events in the ER lumen induced by signals that control B cell differentiation. As our understanding of the molecular details of UPR signaling matures, we are beginning to look to look at other immune cells. Most recently, our studies have begun to examine the UPR in dendritic cells and how this signaling pathway may intersect with the development and function of this critical antigen-presenting cell.
The long-term goal of our research is to establish conceptual basis that will translate into therapeutic manipulation of these responses in the settings of inflammatory and autoimmune diseases and transplantation rejection.