鲁伯埙

教授

复旦大学生命科学学院
Email
luboxun@fudan.edu.cn

Biography

Dr. Lu has been interested in genetic neurological diseases through his whole career. He studied the molecular mechanisms of neuronal excitability regulation and looked for their potential applications in excitability-relevant diseases during PhD at UPenn. His interest then shifted in 2010 to a more challenging type of diseases, neurodegenerative disorders, after he started his postdoc at Novartis and subsequence independent position at Fudan University. During the past six years, his research group has been focusing on Huntington’s Disease (HD), a monogenetic neurodegenerative disorder that has reliable genetic models of different species. One line of investigation is to identify the pathogenic species of mHTT and reveal its fundamental difference with the wild-type protein (wtHTT). He first revealed in human stem cell-derived models that the soluble monomer mHTT is at least one of the major pathogenic species (Lu et al., FASEB J 2013 PMID 23325320). He further demonstrated the “conformational polymorphism” of polyQ of soluble monomeric mHTT but not wtHTT, and identified a toxic mHTT species that is resistant to selective autophagy and thus becomes highly toxic and pathogenic (Fu et al., Nat. Chem. Biol. 2017, PMID 28869595; Sun et al., Autophagy 2017, PMID 28976800; Feng et al., Trends Biochem Sci. 2018, PMID 29636213). A second line of investigation in his group is to perform unbiased screening and cross-species validation for modifiers of mHTT protein levels as potential targets for HD drug development. He has identified a number of highly promising modifiers through this strategy and further demonstrated the druggability for a few of them, including GPR52 and HIPK3 (Lu et al., Nat. Neurosci. 2013, PMID 23525043; Yu et al., Cell Res. 2017, PMID 29151587; Fu et al.; Autophagy 2018, PMID 29130397; Yao et al., eLife 2015, PMID 25738228; Song et al., Brain 2018, PMID 29608652; Al-Ramahi I et al, Cell Syst. 2018, PMID 29936182).