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个人简介
Prof. Bu is a world leader in the field of apoE and apoE receptors, which play critical roles in the pathogenesis of Alzheimer’s disease and related dementias. He has published >350 high impact articles with an H-index of 115, i10-index of 302, and ~40,000 citations (Google Scholar). He has been a “Highly Cited Researcher” according to Web of Science for the past several years. Prof. Bu has received numerous honors and awards including the Zenith Fellows Award from the Alzheimer’s Association, the Established Investigator Award from the American Heart Association, a MERIT award from NIH, the Investigator of the Year award from the Mayo Clinic, and the MetLife Foundation Award for Medical Research in Alzheimer’s disease. He is an elected Fellow of the American Association for the Advancement of Science (AAAS), Founding Editor and Editor-in-Chief of Molecular Neurodegeneration, an Associate Editor for Science Advances, and is on the editorial board for Neuron.
Research Question
Prof. Bu’s primary interest is to understand why APOE4 is a strong genetic risk factor for Alzheimer’s disease and how this gene and related molecular pathways can be targeted for therapy. His interests also extend to addressing the protective mechanisms of APOE2 and APOE rare variants. Among the pathogenic pathways contributing to aging and Alzheimer’s disease, Prof. Bu’s work addresses the roles of brain lipid metabolism, neuronal signaling, neuroimmune focusing on TREM2 and APOE, mechanisms of proteinopathy, and cerebrovascular integrity and function.
Research Approach
APOE and APOE receptor LRPs play critical roles in lipid metabolism, protein trafficking, and signaling. Prof. Bu’s early work using cell biological approaches unraveled the mechanisms of biogenesis and endocytic trafficking of LRP1, a large endocytic receptor with >30 ligands including APOE, amyloid-b (Ab), tau, and a-synuclein, all are critically involved in the pathogenesis of Alzheimer’s and other neurodegenerative diseases. His lab had systematically dissected the cell type-specific function of LRP1 using conditional mouse models as it relates to brain Ab clearance, lipid metabolism, and cerebrovascular function. Prof. Bu’s work also extends to other members of the LDL receptor family including LRP1B and LRP6, as well as insulin receptor. While LRP6 is a key canonical Wnt signaling receptor involved in synaptic function and brain Ab metabolism, the insulin receptor modulates glucose metabolism and mitochondrial functions in aging and Alzheimer’s disease. Prof. Bu’s work in the past 15 years has been focused more on the pathogenic mechanisms of APOE4 using humanized mouse models, as well as induced pluripotent stem cell (iPSC) models including cerebral organoids. Using amyloid model mice, his lab discovered that APOE4 seeds amyloids, considered to be the driving mechanism for the development of Alzheimer’s disease. Using conditional mouse models expressing APOE isoforms in a cell type-specific and inducible manner, Prof. Bu’s lab has also demonstrated the detrimental effects of APOE4 expressed in vascular cells, microglia, or periphery, revealing the multifactorial effects of APOE4 in the pathogenesis of Alzheimer’s disease. Also using humanized APOE mouse models, his lab described the critical role of APOE2 and APOE3-Jacksonville variant in enhancing brain lipid metabolism and cognition, leading to protection against Alzheimer’s disease. Complementing their model system studies, Prof. Bu’s group also utilizes human biospecimens including postmortem brains, cerebral spinal fluid (CSF), and plasma samples to both discover new pathways and biomarkers, and to validate outcomes from model system studies. Prof. Bu’s current work continues to focus on addressing the pathogenic mechanisms of APOE4 and the protective mechanisms of APOE2. His lab is also devoting significant efforts to discovering and developing therapeutics toward APOE and other targets with a goal to prevent and cure Alzheimer’s disease.
Research Question
Prof. Bu’s primary interest is to understand why APOE4 is a strong genetic risk factor for Alzheimer’s disease and how this gene and related molecular pathways can be targeted for therapy. His interests also extend to addressing the protective mechanisms of APOE2 and APOE rare variants. Among the pathogenic pathways contributing to aging and Alzheimer’s disease, Prof. Bu’s work addresses the roles of brain lipid metabolism, neuronal signaling, neuroimmune focusing on TREM2 and APOE, mechanisms of proteinopathy, and cerebrovascular integrity and function.
Research Approach
APOE and APOE receptor LRPs play critical roles in lipid metabolism, protein trafficking, and signaling. Prof. Bu’s early work using cell biological approaches unraveled the mechanisms of biogenesis and endocytic trafficking of LRP1, a large endocytic receptor with >30 ligands including APOE, amyloid-b (Ab), tau, and a-synuclein, all are critically involved in the pathogenesis of Alzheimer’s and other neurodegenerative diseases. His lab had systematically dissected the cell type-specific function of LRP1 using conditional mouse models as it relates to brain Ab clearance, lipid metabolism, and cerebrovascular function. Prof. Bu’s work also extends to other members of the LDL receptor family including LRP1B and LRP6, as well as insulin receptor. While LRP6 is a key canonical Wnt signaling receptor involved in synaptic function and brain Ab metabolism, the insulin receptor modulates glucose metabolism and mitochondrial functions in aging and Alzheimer’s disease. Prof. Bu’s work in the past 15 years has been focused more on the pathogenic mechanisms of APOE4 using humanized mouse models, as well as induced pluripotent stem cell (iPSC) models including cerebral organoids. Using amyloid model mice, his lab discovered that APOE4 seeds amyloids, considered to be the driving mechanism for the development of Alzheimer’s disease. Using conditional mouse models expressing APOE isoforms in a cell type-specific and inducible manner, Prof. Bu’s lab has also demonstrated the detrimental effects of APOE4 expressed in vascular cells, microglia, or periphery, revealing the multifactorial effects of APOE4 in the pathogenesis of Alzheimer’s disease. Also using humanized APOE mouse models, his lab described the critical role of APOE2 and APOE3-Jacksonville variant in enhancing brain lipid metabolism and cognition, leading to protection against Alzheimer’s disease. Complementing their model system studies, Prof. Bu’s group also utilizes human biospecimens including postmortem brains, cerebral spinal fluid (CSF), and plasma samples to both discover new pathways and biomarkers, and to validate outcomes from model system studies. Prof. Bu’s current work continues to focus on addressing the pathogenic mechanisms of APOE4 and the protective mechanisms of APOE2. His lab is also devoting significant efforts to discovering and developing therapeutics toward APOE and other targets with a goal to prevent and cure Alzheimer’s disease.
研究兴趣
论文共 490 篇作者统计合作学者相似作者
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ACTA NEUROPATHOLOGICA COMMUNICATIONSno. 1 (2024)
Gregory Day,Lindsey Kuchenbecker, Philip Tipton,Yuka Martens,Matthew Brier, Nihal Satyadev, Steven Dunham,Evelyn Lazar, Maxwell Dacquel,Rachel Henson,Guojun Bu,Michael Geschwind,
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