Mehdi Jorfi

The Jorfi Lab integrates neuroscience, immunology, and bioengineering to uncover how the immune system contributes to neurodegeneration, with a primary focus on Alzheimer’s disease and related disorders. Once thought to be immune-privileged, the brain is now known to engage in dynamic communication with peripheral immune cells. Our research seeks to decode this neuroimmune crosstalk and determine how it drives—or protects against—neuronal injury. We develop human multicellular “living system” models that serve as human surrogates to model components of the immune system and to probe the mechanisms underlying neural-immune interactions in neurological diseases. These iPSC-derived and microfluidic tissue-chip platforms integrate neurons, astrocytes, microglia, vascular cells, and peripheral immune cells, allowing us to capture disease processes that are hard to study systematically in patients and animals alone. Using these models, coupled with transcriptomic, proteomic, and imaging approaches, we investigate how immune cells (e.g., CD8⁺ T cells) influence glial activation, blood–brain barrier dysfunction, lipid metabolism, and genotype-specific risk factors such as APOE4. Extending these studies to Down syndrome–associated Alzheimer’s disease and progressive multiple sclerosis, we aim to identify actionable immune pathways, circulating biomarkers, and therapeutic strategies to redirect harmful inflammation toward neuroprotection.