bbholmes.bsky.social @bbholmes.bsky.social · 02/06/2026By 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 010
bbholmes.bsky.social @bbholmes.bsky.social · 02/06/2026The 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. 000
bbholmes.bsky.social @bbholmes.bsky.social · 02/06/2026Variants 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...nature.comEarly onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity - npj Dementianpj Dementia - Early onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity 000
bbholmes.bsky.social @bbholmes.bsky.social · 26/01/2026Proud 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/...pnas.orgA cytokine receptor–targeting chimera toolbox for expanding extracellular targeted protein degradation | PNASExtracellular targeted protein degradation (eTPD) is an important new modality for manipulating the extracellular proteome. However, most eTPD rece... 000
bbholmes.bsky.social @bbholmes.bsky.social · 08/09/2025Our 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 #Amyloiddoi.orgβ-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity - Molecular NeurodegenerationTo 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... 032
