By combining patient genetics with biochemical and cellular biology, we hope to transform variant discovery into biological insight and, ultimately, better understanding of neurodegenerative disease. #FTD #Tau #Neurodegeneration #Genomics

The future of precision neurology isn't just finding variants. It's determining what they do. That's the motivation behind the Holmes Lab VUS initiative: building a bedside-to-bench pipeline to functionally interrogate rare patient variants.

Variants of uncertain significance are one of the biggest challenges in neurogenetics. In this work, we identified a previously unreported MAPT mutation in a young patient with rapidly progressive FTD and generated functional evidence supporting pathogenicity. www.nature.com/articles/s44...

Early onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity - npj Dementia

npj Dementia - Early onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity

nature.com

Proud to be a co-author on this new PNAS paper from the Wells Lab. Led by Kaan Kumru, this work expands the kineTAC platform into a versatile cytokine-based toolkit for cell and tissue-selective extracellular protein degradation—a major step forward for precision eTPD. www.pnas.org/doi/10.1073/...

A cytokine receptor–targeting chimera toolbox for expanding extracellular targeted protein degradation | PNAS

Extracellular targeted protein degradation (eTPD) is an important new modality for manipulating the extracellular proteome. However, most eTPD rece...

pnas.org

Our new paper is out! Amyloid plaques switch on microglial GPC4, increasing neuronal tau uptake & toxicity—defining an amyloid→glia→tau pathway & a potential drug target. Pleasure to work with our collaborator @jcoutinhobudd.bsky.social. doi.org/10.1186/s130... #Alzheimers #Glia #Tau #Amyloid

β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity - Molecular Neurodegeneration

To define how Aβ pathology alters microglia function in Alzheimer’s disease, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human micr...

doi.org