Research in the Argon Lab focuses on the role of unfolded protein response (UPR) in combating diseases, such as diabetes and growth retardation. Much of the lab’s research program concerned the control of protein folding in the ER by molecular chaperone and the challenge of quality control of the secretory proteome. The Argon Lab characterized the role of BiP in the normal folding and assembly of immunoglobulin, and how it distinguishes properly folded from misfolded proteins, which are destined for destruction.
The lab team discovered that GRP94, a distinct ER chaperone, is essential for production of antibodies and that it operates with BiP in sequential manner. Both chaperones are hallmarks of the UPR and are also involved in the triage of improperly folded secretory proteins to degradation. The lab investigated the ubiquitin/proteasome pathway of disposal.
More recently, the Argon Lab studied the impact of limiting chaperones and folding enzymes on the protein-folding environment and showed that there are distinct forms of UPR, depending on the type of folding stresses. This led to the discovery of a protein disulfide isomerase whose main function is to interact with and limit the activation of the IRE1 sensor of the UPR, thus guarding against an excessive response that would be detrimental to the cell. This rheostat-like action is due to two distinct enzymatic activities of the IRE1 sensor, that come into play under different times and distinct conditions and underlie the distinct types of UPR seen in various diseases.
Currently the Argon Lab visualizes the dynamics of the IRE1 sensor by live cell imaging as it responds to differentiation signals and to various degrees of stress.
Chief, Division of Cell Pathology
Dr. Argon investigates the unfolded protein response (UPR) , an essential signaling network that determines life or death of stressed cells and tissues. The IRE1 sensor of UPR responds to metabolic stress through four distinct activities and he focuses on determining which stress condition induces each activity and how they are integrated to enable the cells to cope with stress.