Understanding the Microglia Cell-Surface in Alzheimer’s Disease

I will use a combination of proteomics, functional genomics, and protein engineering to understand how human microglia remodel their cell surface in Alzheimer’s Disease.

The microglia surfaceome serves as a critical cellular hub that enables neuroprotective, neurotoxic, and neuroinflammatory signaling in the diseased brain. The ability to precisely target and manipulate diverse microglia states therefore holds tremendous experimental, diagnostic, and therapeutic potential. The proposed project will use innovative technologies to comprehensively define the surfaceome changes of Alzheimer’s disease microglia and will therefore provide the first human cell-surface protein map in this cell type and disease context.

This proposal uses a combination of cutting-edge techniques including iPSC biology, cell-surface proteomics, functional genomics, and antibody engineering to tackle core questions of microglia biology in the context of Alzheimer’s disease. The aims are independent but interwoven to provide the most direct pathway to identifying and targeting disease-relevant proteins.

The focus of my proposal is the identification of novel microglia disease targets and the immediate generation of recombinant antibodies to modulate these proteins. This pipeline directly couples discovery biology to therapeutic development using human iPSC-derived microglia.