Chris Miller

chris.miller@kcl.ac.uk

Website

Research Interests

We are interested in signaling between the endoplasmic reticulum (ER) and mitochondria and how disruption to ER-mitochondria signaling contributes to neurodegenerative changes in Alzheimer’s disease, Parkinson’s disease, and motor neuron disease. This is because ER-mitochondria signaling controls many of the physiological processes that are damaged in these diseases. We are studying the mechanisms by which neurodegenerative disease insults perturb ER-mitochondria signaling and are identifying small molecules that might correct this damage as potential therapeutics for these diseases.

Most significant discovery

We identified an interaction between the ER protein VAPB and the mitochondrial protein PTPIP51 as a mechanism that underlies ER-mitochondria signaling. We showed that the VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease and motor neuron disease.

Educational Interests

Neurodegenerative diseases

Top 4 Publications

Stoica, R., et al 2014. ERmitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nature Comm. 5 3996

Gomez-Suaga, P. et al 2017. The ER-mitochondria tethering complex VAPB-PTPIP51 regulates autophagy. Current Biol. 27 371-385.

Paillusson, S. et al 2017. αSynuclein binds to the ERmitochondria tethering protein V A P B t o d i s r u p t C a 2 + homeostasis and mitochondrial ATP production. Acta Neuropath. 134 129-149

Gomez-Suaga, P. et al 2022. Disruption of ER-mitochondria tethering and signaling in C9orf72-associated ALS/FTD. Aging Cell 21:e13549

Methods / Expertise

• Cell and molecular neuroscience
• Calcium imaging
• Transgenic mouse studies