Matthew J. Simon

Lysosomes cell autonomously regulate myeloid cell states and immune responses

This study shows lysosomal health influences myeloid cell states and immune responses, with Grn deficiency leading to lysosomal dysfunction and specific transcriptional changes in microglia.

Progranulin deficiency perturbs lipid metabolism in white matter microglia

This study shows that PGRN deficiency in microglia affects lipid metabolism, including reduced BMP and PE and increased GalCer, with age-dependent changes in Grn KO mice.

Aquaporin-4 mis-localization slows glymphatic clearance of α-synuclein and promotes α-synuclein pathology and aggregate propagation

This study shows that AQP4 mis-localization impairs glymphatic clearance of α-synuclein and promotes its aggregation and spread in neurodegenerative diseases.

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

This study compares the biodistribution of Fc-engineered molecules targeting BBB receptors with standard antibodies, showing distinct CNS and peripheral organ targeting.

Enhanced legumain activity links progranulin deficiency to TDP-43 pathology in frontotemporal lobar degeneration

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

Rescue of FTLD-associated TDP-43 pathology and neurodegeneration by peripheral AAV-mediated expression of brain-penetrant progranulin

Peripheral AAV-mediated delivery of brain-penetrant PGRN rescues TDP-43 pathology, neurodegeneration and motor phenotypes in FTLD-GRN models.

Targeting Transferrin Receptor to Transport Antisense Oligonucleotides Across the Blood-Brain Barrier

This paper demonstrates that systemically delivered OTV, a TfR-binding molecule, effectively transports ASO across the BBB, achieving widespread and sustained knockdown of target genes in the CNS of mice and non-human primates.

Aquaporin-4 dependent glymphatic solute transport in rodent brain

This study confirms that AQP4 is essential for glymphatic fluid and solute transport in the rodent brain, as Aqp4 disruption reduces CSF influx and amyloid-beta efflux.