Wensheng Lin

Professor, Division of Infectious Diseases and International Medicine

Research Summary

Unfolded Protein Response in Neurological Diseases The research in my laboratory is focused on understanding the effects of the unfolded protein response on neurological diseases and their underlying mechanisms.Endoplasmic reticulum stress, initiated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum lumen, activates an adaptive program known as the unfolded protein response, which coordinates endoplasmic reticulum protein-folding demand with protein-folding capacity and is essential to preserve cell function and survival under stressful conditions. Nevertheless, the unfolded protein response also controls an apoptotic program to eliminate cells whose folding problems in the endoplasmic reticulum cannot be resolved by the adaptive response. In eukaryotic cells, three endoplasmic reticulum–resident transmembrane proteins involved in the unfolded protein response have been identified: pancreatic ER kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). It has become increasingly clear that endoplasmic reticulum stress is an important feature of a number of neurological diseases, such as myelin disorders, neurodegenerative diseases, and brain tumors. Due to the double-edged sword nature of the unfolded protein response, the role that the unfolded protein response plays in these diseases remains ambiguous.Our work utilizes sophisticated mouse models to dissect the precise role of individual branch of the unfolded protein response in myelin disorders, neurodegenerative diseases, and brain tumors. These studies could provide mechanistic insight necessary for designing novel therapeutic strategies for patients with these diseases.