The accumulation of misfolded proteins is a common hallmark of many neurodegenerative diseases (NDDs). These proteins may undergo characteristic biophysical and biochemical changes such as phase separation, phase transition, post-translational modification, and subcellular mislocalization, etc. The Lu group is interested in understanding how these misfolded proteins may eventually lead to NDDs through their biophysical/biochemical changes. More importantly, the group aims to tackle NDDs by targeting these proteins and has developed the novel degrader technology ATTEC (autophagy-tethering compounds) to clear these proteins or even relevant organelles. The group has been focusing on Huntington’s disease (HD), which is a monogenetic NDD caused by a CAG repeat expansion mutation in the exon1 of the HTT gene. The group also expanded the research to other NDDs and strategies to target misfolded proteins. Specially, we are currently exploring these directions:

1.To explore the upstream regulation mechanisms of misfolded proteins by using various genetic and compound screening approaches. (Representative publications: PMID:23525043；PMID:24388390；PMID:25738288；PMID: PMID:29151587；PMID:29608652；PMID:31928144；PMID:33185430)

2.To explore how the misfolded protein is contributing to the disease by studying their conformation “polymorphisms”, post-translational modifications, phase separation and transitions, downstream signaling pathways, etc. (Representative publications: PMID:23325320；PMID:24998512；PMID:28869595；PMID:28976800；PMID:27264314；PMID:29636213；PMID:29936182；PMID:31813995；PMID:32895897；PMID:33505021；PMID:37592155)

3.Totackle misfolded proteins or organelles by novel approaches such as ATTEC. (Representative publications: PMID:24388390；PMID:32416934；PMID:34239073；PMID:34436975；PMID:35238684；PMID:36218065；PMID:37940449；PMID:37266932；PMID:38332048)