Huaxi Xu, China

Xiamen University Institute of Neuroscience
Dr. Huaxi Xu is Honorary Director and Professor at Institute of Neuroscience at Xiamen University, and formally Jeanne & Gary Herberger Leadership Chair and Director of Neuroscience Initiative at Sanford Burnham Prebys Medical Discovery Institute (SBP). Dr. Xu is an expert specialized in the molecular mechanisms of Alzheimer’s disease (AD). His research is focused on the regulation of APP processing and trafficking, and mechanisms of synaptic dysfunction and neurotoxicity induced by proteotoxic beta amyloid and neurofibrillary tangle (NFT) tau components. Dr. Xu’s laboratory has also engaged in pioneering research in investigating novel genes and pathways involved in neuronal function/dysfunction and cell death and integrating their cellular function to the pathogenesis of neurodegenerative diseases such as AD, Down syndrome and Progressive Supranuclear Palsy. To this end, his laboratory is also developing animal models to study neuronal and microglial function in relation to neurodegenerative dysfunction. Dr. Xu has published over 170 papers with a total impact factor of ~1275 (with ~20,000 citations and an h-index >70). Dr. Xu received his Ph.D. degree from Albert Einstein College of Medicine under joint supervision from Dennis Shields and Gunter Blobel (1999 Laureate of the Nobel Prize in Physiology or Medicine); his thesis studies focused on the intracellular trafficking and proteolytic processing of membrane proteins. Dr. Xu completed his postdoctoral studies at The Rockefeller University, where he was appointed assistant professor in 1998 in the laboratory of Paul Greengard (2000 Laureate of the Nobel Prize in Physiology or Medicine), where he carried out a variety of research projects characterizing signal transduction pathways in the central nervous system. Together with Dr. Guojun Bu (Mayo Clinic), Dr. Xu established the well-respected neuroscience journal, Molecular Neurodegeneration (IF=9.599 and instant IF over 12.9), which has become one of the top-ranking scientific journals in the neuroscience field.

Author Of 3 Presentations

ROLES FOR MICROGLIAL ALZHEIMER'S RISK GENES IN REGULATION OF BETA-AMYLOID METABOLISM AND MICROGLIA FUNCTION

Session Name
Session Type
SYMPOSIUM
Date
11.03.2021, Thursday
Session Time
08:00 - 10:00
Room
On Demand Symposia B
Lecture Time
08:45 - 09:00
Presenter
Session Icon
On-Demand

Abstract

Abstract Body

Microglia are increasingly implicated in age-related Alzheimer's disease (AD). Many late-onset AD-related genes are microglia-specific. However, interplay between the AD-related genes in microglia, Aß metabolism and aging remains largely elusive. Recently, we have established isogenic human ES-derived microglia (hMGLs) harboring AD-associated variants in APOE, TREM2, CD33, INPP5D, and SORL1 loci or knockout (KO) by CRISPR/Cas9 gene editing, and through induced differentiation and subsequent treatments with aged human serum. We carry out multi-omics studies including RNAseq, ATACseq, ChIPseq, and proteomics to systematically evaluate the correlations among aging, Aß metabolism and AD-related genes. Moreover, we functionally characterize hMGLs in vitro and in vivo, such as responses to various physio/pathological stimuli, Aβ phagocytosis, and AD-like phenotypes in AD model mice through xenotransplantation. In our preliminary study, we have established the microglial aging model by adding aged human serum in culture and generated hMGLs harboring the AD-associated TREM2 mutant R47H. AD-like expression signatures were observed in TREM2-R47H hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicated that APOE was a convergent pathogenic node. AD-associated TREM2-R47H can enhance APOE expression and impair hMGLs Aβ uptake in an APOE-dependent manner. Xenotransplants of TREM2-R47H hMGLs reduced Aβ uptake/clearance in the brain of AD mice. Moreover, we found that AD-associated gene expression landscape significantly altered during microglial aging. Our study shall provide new insights into the contribution of microglial aging and the interplay between aging, Aß metabolism and AD genes in microglia to AD pathogenesis, and may identify new strategies for AD therapeutics.

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Presenter of 3 Presentations

ROLES FOR MICROGLIAL ALZHEIMER'S RISK GENES IN REGULATION OF BETA-AMYLOID METABOLISM AND MICROGLIA FUNCTION

Session Name
Session Type
SYMPOSIUM
Date
11.03.2021, Thursday
Session Time
08:00 - 10:00
Room
On Demand Symposia B
Lecture Time
08:45 - 09:00
Presenter
Session Icon
On-Demand

Abstract

Abstract Body

Microglia are increasingly implicated in age-related Alzheimer's disease (AD). Many late-onset AD-related genes are microglia-specific. However, interplay between the AD-related genes in microglia, Aß metabolism and aging remains largely elusive. Recently, we have established isogenic human ES-derived microglia (hMGLs) harboring AD-associated variants in APOE, TREM2, CD33, INPP5D, and SORL1 loci or knockout (KO) by CRISPR/Cas9 gene editing, and through induced differentiation and subsequent treatments with aged human serum. We carry out multi-omics studies including RNAseq, ATACseq, ChIPseq, and proteomics to systematically evaluate the correlations among aging, Aß metabolism and AD-related genes. Moreover, we functionally characterize hMGLs in vitro and in vivo, such as responses to various physio/pathological stimuli, Aβ phagocytosis, and AD-like phenotypes in AD model mice through xenotransplantation. In our preliminary study, we have established the microglial aging model by adding aged human serum in culture and generated hMGLs harboring the AD-associated TREM2 mutant R47H. AD-like expression signatures were observed in TREM2-R47H hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicated that APOE was a convergent pathogenic node. AD-associated TREM2-R47H can enhance APOE expression and impair hMGLs Aβ uptake in an APOE-dependent manner. Xenotransplants of TREM2-R47H hMGLs reduced Aβ uptake/clearance in the brain of AD mice. Moreover, we found that AD-associated gene expression landscape significantly altered during microglial aging. Our study shall provide new insights into the contribution of microglial aging and the interplay between aging, Aß metabolism and AD genes in microglia to AD pathogenesis, and may identify new strategies for AD therapeutics.

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Moderator of 1 Session

LIVE SYMPOSIUM DISCUSSION

LIVE DISCUSSION - DISEASE MECHANISMS, PATHOPHYSIOLOGY: ASTROCYTES, NEUROINFLAMMATION, MICROGLIA

Date
13.03.2021, Saturday
Session Time
16:30 - 17:00
Session Icon
Live