Experimental Neuropathology Lab

The challenge

Dysregulated glia-mediated neuroinflammatory processes have been implicated in most neurodegenerative diseases, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. There is growing interest in treating these conditions with CNS-penetrating immunotherapies. Our working hypothesis is that the way the brain responds to insults is equally relevant to long-term outcomes as the insult itself.

A prototypical example of dysregulated glia-mediated neuroinflammation is multiple sclerosis, the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system, affecting individuals from young adulthood. While existing disease-modifying treatments effectively control peripheral immune responses and mitigate the relapse-associated inflammatory activity, they demonstrate limited efficacy in halting disease progression that occurs independently of relapses. Preventing or treating clinical progression is a major unmet need in multiple sclerosis. Growing evidence supports the role of compartmentalized inflammation within the leptomeninges and within the parenchyma, as occurring in chronic active lesions, in clinical progression. The recent possibility to image in vivo chronic active lesions in the brain (as paramagnetic rim lesions using susceptibility-based MRI) led to the recent discovery of their important role in driving early disability accrual and potentially progression.

Main Research Areas

Decoding glia-mediated chronic inflammation

Using advanced neuropathological multi-omic techniques, combining single-cell transcriptomics, spatial transcriptomics, multiplex immunostaining, and metabolomics of human autopsy brain and spinal cord tissues.

Cellular modeling of the glia interactome

Using human-induced pluripotent stem cell (hiPSC) glia-enriched neural organoids to investigate human neuron-glia-microglia functional crosstalk and to identify and test relevant, druggable molecular mechanisms of chronic inflammation.

Translational platform using in vivo MRI and fluid biomarkers

Validate the discovered key mechanisms of glia-mediated chronic inflammation in individuals with neurological diseases and to design novel proof-of-concept, biomarker-based clinical trials.