Li-Huei Tsai (United States of America)
Massachusetts Institute of Technology
Brain and Cognitive Sciences
Professor Li-Huei Tsai is the Director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, a Picower Professor of Neuroscience, and an Associate Member of the Broad Institute. Tsai is interested in elucidating the pathogenic mechanisms underlying neurological disorders that impact learning and memory. She uses multi-omic approach to decipher the pathophysiology of Alzheimer’s dementia (AD). Her team pioneered the use of patient-derived induced pluripotent stem cells (iPSCs) to produce various brain cell types and a novel 3D brain tissue model (miBrain) inclusive of a biomimetic BBB, myelinated neurons, and immune components to model AD pathology. She also pioneered the use of non-invasive sensory stimulation to treat AD. Tsai is a Fellow of the American Association for the Advancement of Science, a Fellow of the National Academy of Inventors, a Member of the National Academy of Medicine, an Academician of the Academia Sinica in Taiwan, and a Member of the American Academy of Arts and Sciences. She is a recipient of the Mika Salpeter Lifetime Achievement Award, and the 2018 Hans Wigzell Research Foundation Science Prize for her research on Alzheimer’s disease. In 2022 she was named a Visiting Professor of the Vallee Foundation.

Moderator of 1 Session

 Conference Calendar

IMMUNITY AND INFLAMMATION IN NEURODEGENERATION

Session Time
08:40 - 10:40
Session Type
SYMPOSIUM
Date
Wed, 06.03.2024
Room
Auditorium II
Chair(s)

Presenter of 2 Presentations

 Conference Calendar

SINGLE CELL DISSECTION OF DEMENTIA PATHOGENESIS

Session Name
2170 - PRE CONFERENCE SYMPOSIUM 01: CREATING MEANING OUT OF CHAOS: LINKING BIG DATA TOOLS TO PATHOPHYSIOLOGY, BIOMARKERS, DIAGNOSES AND CLINICAL STUDIES (ID 1)
Session Type
PRE CONFERENCE SYMPOSIUM
Date
Tue, 05.03.2024
Session Time
08:00 - 15:30
Room
Auditorium VI+VII
Presenter
Lecture Time
08:15 - 08:35

Abstract

Abstract Body

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. Altered microglial states affect neuroinflammation, neurodegeneration, and disease, but remain poorly understood. We have generated single cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from post-mortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. We uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Moreover, we analyzed 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects, and diverse Alzheimer’s disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,699 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Overall, we provide new insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.
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SINGLE CELL GENOMICS REVEALS HUMAN MICROGLIAL STATE TRANSITION IN ALZHEIMER’S DISEASE PROGRESSION”

Session Name
2750 - IMMUNITY AND INFLAMMATION IN NEURODEGENERATION (ID 17)
Session Type
SYMPOSIUM
Date
Wed, 06.03.2024
Session Time
08:40 - 10:40
Room
Auditorium II
Presenter
Lecture Time
08:40 - 08:55

Abstract

Abstract Body

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. Altered microglial states affect neuroinflammation, neurodegeneration, and disease, but remain poorly understood. We have generated single cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from post-mortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. We uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Moreover, we analyzed 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects, and diverse Alzheimer’s disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,699 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Overall, we provide new insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.

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