Paul John Whiting

Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis

This study shows that PSEN1 mutations disrupt regulated intramembrane proteolysis in astrocytes, leading to enhanced inflammatory responses and contributing to familial Alzheimer's disease progression.

Sodium channel inhibitors alter the progress of tangle development in a mouse model of dementia

This study investigates the effect of sodium channel inhibitors on plaque and tangle development in Alzheimer's mouse models, finding reduced tangle density with inhibitor treatment.

The hypermorphic PLCγ2 S707Y variant dysregulates microglial cell function: insight into PLCγ2 activation in brain health and disease, and opportunities for therapeutic modulation.

This study investigates the effects of the PLCγ2 S707Y hypermorphic variant on human microglia, showing increased enzymatic activity but reduced phagocytosis and cytokine production, and suggests therapeutic strategies should mimic the beneficial effects of the P522R variant.

A primary rodent triculture model to investigate the role of glia-neuron crosstalk in regulation of neuronal activity.

This paper develops a triculture model of neurons, astrocytes, and microglia to study glia-neuron interactions and their impact on neuronal activity and synapse function.

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at Chr16q11.2 and on the MAPT H1 allele

The paper identifies KAT8 and KANSL1 as regulators of PINK1-mitophagy linked to Parkinson's disease risk, suggesting a novel pathway for therapeutic targeting.

Microglial expression of the Wnt signalling modulator DKK2 differs between human Alzheimer's disease brains and mouse neurodegeneration models

This study compares microglial DKK2 expression in mouse AD models and human AD brains, finding upregulation in mice but not in humans.

Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters

The paper identifies Sirt2-induced H4K16ac deacetylation of Fzd1 and Fzd7 promoters as a mechanism repressing Wnt signaling in Alzheimer's disease.

Alzheimer’s disease Phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph

The paper confirms that the PLCG2 P522R variant is protective against Alzheimer’s disease and shows it weakly activates PLCG2 enzyme function in microglia.

Molecular and functional variation in iPSC-derived sensory neurons

The paper maps regulatory variants in iPSC-derived sensory neurons, identifying genetic influences on gene expression, chromatin accessibility, and RNA splicing, with overlaps to disease associations.