Matthew G. Holt

Directed disruption of IL2 aggregation sites produces designer biologics with enhanced specificity coupled to improved production capacity

This paper designs IL2 muteins with enhanced Treg or CD8 T cell specificity and improved production by predicting mutations using SolubiS and testing their functional and structural properties.

The astrocyte alpha 1-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex.

This study investigates the role of astrocyte 1A-adrenoreceptors in noradrenergic signaling in mouse visual cortex, finding they regulate calcium transients and synaptic plasticity.

Traumatic brain injury modifies adult hippocampal neural stem cell fate to promote neurogenesis at the cost of astrogliogenesis.

This study shows that traumatic brain injury shifts adult hippocampal neural stem cell fate toward neurogenesis and away from astrogliogenesis, using single-cell RNA sequencing and spatial transcriptomics.

Unravelling cell type specific response to Parkinson's Disease at single cell resolution

The paper analyzes single-cell transcriptomics data from Parkinson's Disease patients and controls to identify cell type-specific molecular responses and pathways involved in neurodegeneration.

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain

This study shows that delivering IL2 to the brain in aging mice partially restores molecular signatures of aging and improves spatial learning.

A conformational switch controlling the toxicity of the prion protein

This study identifies an H-latch conformational switch in PrPC that drives prion toxicity and shows that disrupting this switch can protect against prion-related neurodegeneration.

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's Disease

The paper shows that astrocyte calcium dysfunction leads to early network hyperactivity in Alzheimer's Disease, which can be reversed by restoring calcium signaling.

Molecularly distinct astrocyte subpopulations spatially pattern the adult mouse brain

The paper identifies molecularly distinct astrocyte subpopulations in the adult mouse brain and shows their spatial distribution has functional implications.

AAV mediated delivery of a novel anti-BACE1 VHH reduces Abeta in an Alzheimer’s disease mouse model

The paper demonstrates that AAV-delivered VHH-B9 reduces amyloid beta levels in an Alzheimer’s disease mouse model.

Flexible, fast and selective genetic manipulation of the vertebrate CNS with misPiggy

The paper introduces a transposon-based system for genetic manipulation of the vertebrate CNS, enabling long-term conditional experiments across cell types and species.

Astrocytes integrate local sensory and brain-wide neuromodulatory signals.

The paper shows astrocytes in mouse visual cortex integrate local visual signals with arousal state through Ca2+ transients.

Post-transcriptional modulation of Dscam1 enhances axonal growth in development and after injury

This study identifies a conserved signaling pathway involving Dscam1, Faf/Usp9x, and JNK that promotes axonal growth in Drosophila and mammals after CNS injury.