MICROENVIROMENT-DRIVEN PATHOGENESIS AND TRANSLATIONAL THERAPEUTICS IN SYNUCLEINOPATHIES

Our lab explores the complex multi-cellular communication networks driving neurodegeneration, with a primary focus on devastating orphan conditions like Multiple System Atrophy (MSA). Given the rapid progression and striking lack of disease-modifying therapies for these disorders, our team strategically moves beyond the traditional neuron-centric paradigm. Instead, we investigate how lipid metabolism dysregulation in glial cells shapes a highly toxic brain microenvironment. 

Specifically, we decode how specialized lipid-binding proteins in astrocytes sort and export toxic lipid species via extracellular vesicles, triggering non-cell-autonomous ferroptosis and inflammatory cascades in neighboring vulnerable oligodendrocytes. Concurrently, we are mapping the intricate cell-surface receptor networks and adaptor proteins that facilitate the transcellular propagation and pathological endocytosis of toxic protein aggregates. To achieve this, we employ a multidisciplinary approach combining high-fidelity in vivo transgenic models, spatial transcriptomics, and single-cell spatiotemporal trajectory analysis. Bridging fundamental mechanisms with clinical translation, our team is aggressively developing a robust, proprietary pipeline of highly brain-penetrant small molecule probes. By precisely targeting these lipid-driven pathologies, we aim to intercept the disease at its upstream microenvironmental source, ultimately translating our bench discoveries into viable clinical therapeutics.