We are working on new strategies for organ protection by boosting highly conserved signaling pathways that Nature has designed to protect cells from various forms of stress-induced damage. Small ubiquitin-like modifier (SUMO1-3) conjugation is an archetypical signaling pathway that is known to protect cells from various kinds of stress. Our data support the notion that targeting SUMO conjugation is a promising new strategy for protecting organs in the clinical setting.Our long-term goal is to improve outcomes in patients who suffer a stroke or other forms of brain ischemic injury.
Subramonian D, Raghunayakula S, Olsen JV, Beningo KA, Paschen W, Zhang X-D. Analysis of changes in SUMO2/3 modification during breast cancer progression and metastasis. J Proteome Res; 29 Jul 2014; DOI: 10.1021/pr500119a.
Wang L, Wansleeben C, Zhao S, Miao P, Paschen W, Yang W. SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development. EMBO Rep. 2014;15:878-885.
Iwabuchi M, Sheng H, Thompson JW, Wang L, Debois LG, Gooden D, Moseley MA, Paschen W, Yang W. Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia. J Cereb Blood Flow Metabol. 2014;34:425-432.
Yang W, Sheng H, Thompson JW, Zhao S, Wang L, Miao P, Liu X, Moseley MA, Paschen W. Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways. Stroke. 2014;45:1115-1122.
Wang L, Rodriguiz RM, Wetsel WC, Sheng H, Zhao S, Liu X, Paschen W, Yang W. Neuron-specific SUMO1-3 knockdown in mice impairs episodic and fear memories. J Psychiatry Neurosci. 2014;39:259-266.
Yang W, Wang L, Paschen W. Development of a high-throughput screening assay for inhibitors of small ubiquitin-like modifier proteases. J Biomol Screen. 2013;18:621-628.
Yang W, Wang L, Roehn G, Pearlstein RD, Ali-Osman F, Pan H, Goldbrunner R, Krants M, Harms C, Paschen W. Small ubiquitin-like modifier 1-3 conjugation is activated in human astrocytic brain tumors and is required for glioblastoma cell survival. Cancer Sci. 2013;104:70-77.
Wang L, Ma Q, Yang W, Mackensen GB, Paschen W. Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons. J Neurochem. 2012;123:349-359.
Yang W, Thompson JW, Wang Z, Wang L, Sheng H, Foster MW, Moseley MA, Paschen W. Analysis of oxygen/glucose-deprivation-induced changes in SUMO3 conjugation using SILAC-based quantitative proteomics. J Proteome Res. 2012;11:1108-1117.
Datwyler AL, Laettig-Tuennemann G, Yang W, Paschen W, Lee SL, Dirnagl U, Endres M, Harms C. SUMO2/3 conjugation is an endogenous neuroprotective mechanism. J Cereb Blood Flow Metabol. 2011;31:2152-2159.
Yang W, Ma Q, Mackensen GB, Paschen W. Deep hypothermia markedly activates the small ubiquitin-like modifier conjugation pathway; implications for the fate of cells exposed to transient deep hypothermic cardiopulmonary bypass. J Cereb Blood Flow Metabol. 2009;29:886-890.
Yang W, Sheng H, Homi HM, Warner DS, Paschen W. Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation – a new target for therapeutic intervention? J Neurochem. 2008;106:989-999.
Yang W, Sheng H, Warner DS, Paschen W. Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation. J Cereb Blood Flow Metabol. 2008;28:892-896.
Yang W, Sheng H, Warner DS, Paschen W. Transient global cerebral ischemia induces a massive increase in protein sumoylation. J Cereb Blood Flow Metabol. 2008;28:269-279.