Wensheng Lin, MD, PhD

Associate Professor, Department of Neuroscience

Wensheng Lin

Contact Info

linw@umn.edu

Office Phone 612-626-5079

Office Address:
4-140 WMBB

Lab Address:
4-240 WMBB

Research

Research Summary/Interests

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.

Publications

Yue, Y, Stanojlovic, M, Lin, Y, Karsenty, G & Lin, W 2019, 'Oligodendrocyte-specific ATF4 inactivation does not influence the development of EAE' Journal of Neuroinflammation, vol. 16, no. 1, 23. https://doi.org/10.1186/s12974-019-1415-6

Chen, Y, Podojil, JR, Kunjamma, RB, Jones, J, Weiner, M, Lin, W, Miller, SD & Popko, B 2019, 'Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis' Brain, vol. 142, no. 2, pp. 344-361. https://doi.org/10.1093/brain/awy322

Yue, Y, Stone, S & Lin, W 2018, 'Role of nuclear factor ?b in multiple sclerosis and experimental autoimmune encephalomyelitis' Neural Regeneration Research, vol. 13, no. 9, pp. 1507-1515. https://doi.org/10.4103/1673-5374.237109

Stone, SM, Wu, S, Jamison, S, Durose, WW, Pallais, JP & Lin, W 2018, 'Activating transcription factor 6? deficiency exacerbates oligodendrocyte death and myelin damage in immune-mediated demyelinating diseases' GLIA, vol. 66, no. 7, pp. 1331-1345. https://doi.org/10.1002/glia.23307

Stone, SM, Jamison, S, Yue, Y, Durose, WW, Schmidt-Ullrich, R & Lin, W 2017, 'NF-?B activation protects oligodendrocytes against inflammation' Journal of Neuroscience, vol. 37, no. 38, pp. 9332-9344. https://doi.org/10.1523/JNEUROSCI.1608-17.2017

Lin, W 2017, 'Neuroprotective effects of vascular endothelial growth factor A in the experimental autoimmune encephalomyelitis model of multiple sclerosis' Neural Regeneration Research, vol. 12, no. 1, pp. 70-71. https://doi.org/10.4103/1673-5374.198982

Jiang, M, Liu, L, He, X, Wang, H, Lin, W, Wang, H, Yoon, SO, Wood, TL & Lu, QR 2016, 'Regulation of PERK-eIF2? signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes' Nature Communications, vol. 7, 12185. https://doi.org/10.1038/ncomms12185

Ho, Y, Li, X, Jamison, S, Harding, HP, McKinnon, PJ, Ron, D & Lin, W 2016, 'PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis' American Journal of Pathology, vol. 186, no. 7, pp. 1939-1951. https://doi.org/10.1016/j.ajpath.2016.03.004

Stanojlovic, M, Pang, X, Lin, Y, Stone, SM, Cvetanovic, M & Lin, W 2016, 'Inhibition of vascular endothelial growth factor receptor 2 exacerbates loss of lower motor neurons and axons during experimental autoimmune encephalomyelitis' PloS one, vol. 11, no. 7, e0160158. https://doi.org/10.1371/journal.pone.0160158

Lim, S, Liu, H, Da Silva, LM, Arora, R, Liu, Z, Phillips, JB, Schmitt, DC, Vu, T, Mcclellan, S, Lin, Y, Lin, W, Piazza, GA, Fodstad, O & Tan, M 2016, 'Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1a' Cancer Research, vol. 76, no. 8, pp. 2231-2242. https://doi.org/10.1158/0008-5472.CAN-15-1538