Dr Shane Liddelow - NYU Grossman School of Medicine

Dr Shane Liddelow - NYU Grossman School of Medicine

Location: 
Online
Start Time: 
Fri, 12/08/2022 - 9:30am
End Time: 
Fri, 12/08/2022 - 10:30am

WEHI Parkinson’s Disease Special Seminar hosted by Associate Professor Grant Dewson & Dr Sylvie Callegari

Dr Shane Liddelow

Neuroscience Institute NYU Grossman School of Medicine; Depts of Neuroscience & Physiology, and of Ophthalmology, NYU Grossman School of Medicine; Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine

Reactive astrocyte heterogeneity in inflammation and disease

 

Join via ZOOM

Webinar ID: 872 6613 1802

Passcode: 274045

Including Q&A session

 

The study of astrocyte reactivity requires careful identification of heterogeneity via transcriptomic profiling, followed by identification using cell based systems to model their functional alterations compared to physiologically ‘normal’ astrocytes. Further validation by confirmation in rodent models of disease and in human cells and postmortem tissue provides corroboration of biologically important reactive astrocyte sub-states. We recently completed a large well-powered scRNAseq analysis of astrocyte reactivity profiles following acute systemic inflammation, highlighting several transcriptomically defined sub-states. Further, using integration with other published datasets we find specific disease-associated sub-states in rodent models of Alzheimer’s disease, demyelination, and an acute stab wound. Following, we produced in vitro models to further study the functional alterations of these sub-states of reactive astrocytes, and used snRNASeq from human post-mortem Alzheimer’s disease patients for cross-specific integration.

In parallel studies, we used animal models of neurodegeneration: the bead occlusion model of glaucoma, and the SOD1G93A model of amyotrophic lateral sclerosis to highlight two key insights. First, we report that neurons must be susceptible to astrocyte-mediated cell death; and second, disease-associated mutations alone may not mediate reactivity states, but instead lower their threshold for ‘activation’. Combined these studies highlight the importance of functional validation of transcriptomic ally defined reactive astrocyte sub-states, and identify a specific set of stop-gaps in the mechanism of reactive astrocyte mediated neurotoxicity.

 

All welcome!