Current Projects
Project 1 focuses on targeted delivery of macrophage membrane coated nanoparticles to inflamed nerves in the experimental autoimmune neuritis model of Guillain-Barre syndrome.
To assess the fate of nanoparticles in nerves, we covalently attach spectrally defined quantum dots to the polymer core. This enables precise tracking of nanoparticles within the microvasculature and endoneurial compartment. Conventional fluorophores leak out of particles and complicate analysis (ask us how we know!).
Project 2 investigates blood nerve barrier permeability and immune cell infiltration in the connexin32 knockout mouse model of Charcot Marie Tooth disease type 1X. Given the inflammatory phenotypes that are observed, we hypothesize that our membrane coated nanoparticles will target affected nerves in CMT1X as well.
We use the CCR2:CCL2 signalling axis to target nanoparticles to nerves. We have found that macrophages are not a viable source of plasma membrane vesicles for targeting (again- ask us how we know!). The experimental workflow utilizes monocytes as a CCR2-rich source of material for functionalization.
Project 3 explores different potential anti-inflammatory payloads. Statins and prenyltransferase inhibitors attenuate chemokine release from peripheral nerve endothelial cells and therapeutically attenuate several different preclinical models of autoimmune inflammatory disease. Several statins of interest exist as hydrophobic prodrugs or hydroxyacid active metabolites, enabling efficient loading into polymeric nanoparticles or membrane vesicles.
We use statins as both a model payload (to assess how nerve targeting affects organ and nerve PK/PD) and a potential therapeutic (building on previous evidence that lovastatin protectively and therapeutically attenuates EAN).