Dominic Simpson | DPhil Student
PubMed Publications

I am engaged in elucidating the role of Oxidation Resistance 1 (OXR1) in the regulation of the vacuolar (V-type) ATPase proton pump. OXR1 is a member of the TLDc family of proteins, which share a common C-terminal domain that gives this family its name. This protein family, which includes OXR1, Nuclear Receptor Coactivator 7 (NCOA7), and TBC1D24, plays an indispensable role in safeguarding neuronal survival in the mammalian brain.

While the specific neuroprotective mechanisms of these proteins remain a puzzle, recent findings have unveiled their association with the V-ATPase, a critical player in cellular function, including phagocytosis and neurotransmission. Notably, OXR1 exhibits robust expression in human microglia, and the absence of this protein triggers neuroinflammation. This condition is marked by neuronal death, pronounced microglial activation and astrocyte infiltration.

My aim is to decipher the mechanisms through which OXR1 governs V-ATPase activity in microglia, as the resident immune cells of the brain. To achieve this, I employ an array of molecular biology tools in our hiPSC-derived microglia, including CRISPR-Cas9 and lentiviral transduction. By probing these intricate pathways, I aim to contribute to our understanding of the crucial interplay between OXR1 and V-ATPase, shedding light on the broader spectrum of neuroprotection within the human brain.

Outside of the lab I love hiking, cooking and reading. I’m also currently learning German… bis später!

Artwork produced by Jack Brougham. Funding awarded by the ARUK Thames Valley Network.