- MD, University of Virginia, 2018
- PhD, University of Virginia, 2016
Education & Training
Our overarching goal is to better understand the mechanisms of neuroimmune and neurodegenerative disorders, with an emphasis on progressive multiple sclerosis, to better treat these conditions. We use unbiased, high throughput assays on patient samples to discover targets and pathways that we then study mechanistically with appropriate animal or cell models.
A protein we have longstanding interest in the alarmin interleukin 33 (IL-33). This is a nuclear cytokine expressed in the healthy CNS and released upon injury or stress to “alert” the immune system and trigger wound healing pathways. The lab is currently studying the impact of IL-33 signaling on glial cells using knockout mice, primary cell culture, and putative therapeutic small molecules.
Another project is focused on understanding how inflammation in the meninges impacts the underlying brain. While mostly thought of as a white matter disease, MS also leads to demyelination, neuron death, and microglia activation in the grey matter. The extent of grey matter involvement closely correlates with cognitive impairment, fatigue, and depression, but we have no therapies to target this aspect of the disease. We are currently generating spatial transcriptomic datasets to better understand underlying mechanisms here.
Mace JW*, Gadani SP*, Smith MD, Galleguillos D, Kang BG, Roy M, Liu M, Summers B, Garton T, Gharagozloo M, Gill AJ, Pardo CA, Sotirchos ES, Dawson VL, Dawson TM, Calabresi PA. Autoimmune neuroinflammation leads to neuronal death via MIF nuclease-mediated parthanatos. Nature Neuroscience. 2026;29:796–809. *Co-first author.
Garton T, Gadani SP, Gill AJ, Calabresi PA. Neurodegeneration and demyelination in multiple sclerosis. Neuron. 2024.
Gadani SP, Singh S, Kim S, Smith MD, Calabresi PA, Bhargava P. Spatial transcriptomics of meningeal inflammation reveals variable penetrance of inflammatory gene signatures into adjacent brain parenchyma. eLife. 2023.
Gadani SP, Reyes-Mantilla M, Jank L, Harris S, Douglas M, Smith MD, Calabresi PA, Mowry EM, Fitzgerald KC, Bhargava P. Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy. EBioMedicine. 2021;73:103636.
Gadani SP, Smirnov I, Smith AT, Overall CC, Kipnis J. Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury. Journal of Experimental Medicine. 2017;214(2):285–296.
Gadani SP, Walsh JT, Smirnov I, Zheng J, Kipnis J. The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron. 2015;85(4):703–709.
Full list of publications: https://scholar.google.com/citations?user=RTnqJjAAAAAJ&hl=en
