Title
Assistant Professor
Ph.D.
University of Connecticut
Post Doctoral Training
University of Cambridge
Major Interests
Glia are specialized cells of the brain and spinal cord that act to maintain homeostatic processes via a coordinated network. Within these networks, glial nodes function as ‘metabolic hubs’ for the uptake, clearance, and processing of extracellular metabolic (toxic) waste. Through the expression of complex biochemical pathways, they can inactivate and repurpose this waste into energy substrates and building blocks that are then re-distributed throughout the network to surrounding cells. Well-regulated metabolic function is necessary for glia to sustain these metabolic and biochemical processes to avoid an accumulation of neurotoxic and cytotoxic factors. In neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, glia undergo metabolic remodeling that disrupts these supply networks and sustains their inflammatory reactivity that contributes to the slow but progressive spread of tissue damage. However, the identity of the metabolic regulators underlying these processes is incomplete. The lab aims to identify these metabolic regulators in glia which disrupts these networks that promote neurodegeneration towards the discovery of therapeutic interventions. Leveraging CRISPR/Cas9 screens, in vivo preclinical models, and human stem cell modelling of glial function the lab will explore:
- The role of glial networks in regulating inflammatory activity in neurodegenerative disease
- Metabolic regulators of inflammatory glial reactivity in neuroinflammation and demyelination
- Targeting of glial networks to reduce neuroinflammation and restore homeostatic functioning
Office: Biomedical Research Building II, Room 562-2
Slot 846
Publications
1) Peruzzotti-Jametti L*, Willis CM*, Krzak G*, Hamel R, Pirvan L, Ionescu B, Reisz JA, Prag HA, Garcia-Segura ME, Wu V, Xiang Y, Barlas B, Casey A, van den Bosch AMR, Nicaise AM, Roth L, Bates GR, Huang H, Prasad P, Vincent AE, Frezza C, Viscomi C, Balmus G, Takats Z, Marioni JC, D’Alessandro A, Murphy MP, Mohorianu I, Pluchino S. “Mitochondrial complex I activity in microglia sustains neuroinflammation.” Nature. 2024. PMID: 38480879
2) Sutter PA*, Willis CM*, Menoret A, Nicaise AM, Sacino AV, Sikkema AH, Jellison ER, Win KK, Han DK, Church W, Baron W, Vella ATJ, Crocker SJ. “Astrocytic TIMP-1 regulates production of Anastellin, a novel inhibitor of oligodendrocyte differentiation and FTY720 responses.” PNAS. 2024. PMID: 38266047
3) Willis CM, Nicaise AM, Menoret A, Ryu JK, Mendiola AS, Jellison ER, Givogri MI, Han DK, Bongarzone ER, Akassoglou K, Vella AT, Crocker SJ. “Exosomal Fibrinogen Induces a CD8-mediated Relapsing-Remitting Disease Phenotype in a MOG-EAE Model of Demyelination.” PNAS. 2019. PMID: 31068461