Xianlin Han, PhD

Our research focuses on functional lipidomics, that is, uncovering alterations in lipid metabolism, signaling, and homeostasis that occur under patho(physio)logical conditions such as Alzheimer’s disease (AD) and aging by lipidomics; identifying the underlying molecular and biochemical mechanisms; unraveling the biological consequences resulted due to these lipid changes; and developing drug targets for the diseases based on the mechanistic and consequence studies. Lipidomics, which facilitates large-scale analysis of cellular lipidomes based on the principles and techniques of analytical chemistry, allows us to comprehensively and effectively determine alterations in lipid metabolism, signaling, and homeostasis of tissue samples or an entire organ under different conditions.

Our laboratory is one of the world-leading research groups on lipidomics. We have developed an enabling technology with in-house software programs termed “multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL)”, initiated in the early 1990s and still under constant development. The MDMS-SL technology provides modular, robust, and label-free quantification of lipids. At its current stage, the technology enables us to identify and quantify over 50 lipid classes, over 95% of lipid mass content, and thousands of individual lipid molecular species from limited amounts of biological samples in an accurate (>90% reproducibility) and relatively high throughput fashion.

Our lab research currently focuses on identification of molecular mechanisms underlying AD pathogenesis driven by brain myelin disruption. By using lipidomics, our previous studies demonstrated the severe loss of sulfatide (a class of myelin lipids) in the earliest clinically-recognizable stages of AD. Our mechanistic studies revealed that all the major risk factors for AD lead to the reduction of sulfatide content in the brain. Our recent work revealed that deficiency in sulfatide leads to almost all adult-onset AD-like phenotypes (e.g., cognitive decline, gliosis and neuroinflammation, Abeta pathology, tau pathology, disrupted urinary control, ventricular enlargement, etc.) by using both constitutive sulfatide-depleted and myelinating cell-specific conditional sulfatide-deficient mouse models. The findings allow us to identify potential novel therapeutic target(s) for treatment of AD in our ongoing translational studies.

1. He, S., Mittra, N., Bao, H., Bhattacharjee, A., Dodds, S.G., Dupree, J.L., and Han, X. (2026) Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of Trem2-mediated microglial activation. Nat. Commun. 17, 338. doi: 10.1038/s41467-025-66222-9. PMCID: PMC12789058.
2. Xu, Z., Shabestari, S.K., Barannikov, S., Bieniek, K.F., Blurton-Jones, M., Palavicini, J.P., and Han, X. (2025) Microglia-specific regulation of lipid metabolism in Alzheimer’s disease revealed by microglial depletion in 5xFAD mice. Nat. Commun. 16, 9156, doi: 10.1038/s41467-025-64161-z. PMC12528747.
3. He, S., Li, X., Mittra, N., Bhattacharjee, A., Wang, H., Zhao, S., Liu, F., and Han, X. (2025) Microglial cGAS deletion preserves intercellular communication and alleviates amyloid-β-induced pathogenesis of Alzheimer’s disease. Adv. Sci. 12, e2410910. doi: 10.1002/advs.202410910. PMCID: PMC11948024.
4. He, S., Xu, Z., and Han, X. (2025) Lipidome disruption in Alzheimer’s disease brain: Detection, pathological mechanisms, and therapeutic implications. Mol. Neurodeger. 20, 11. doi: 10.1186/s13024-025-00803-6. PMC11773937.
5. Xu, Z., He, S., Begum, M.M., and Han, X. (2024) Myelin lipid alterations in neurodegenerative diseases: Landscape and pathogenic implications. Antioxid. Redox Signal. 41, 1073-1099. doi: 10.1089/ars.2024.0676. PMC11971557.
6. He, S., Qiu, S., Pan, M., Palavicini, J.P., Wang, H., Li, X., Bhattacharjee, A., Barannikov, S., Bieniek, K.F., Dupree, J.L., and Han, X. (2023) Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer’s disease. Clin. Trans. Med. 13, e1332. Doi: 10.1002/ctm2.1332. PMCID: PMC10361545.
7. Dustin, E., McQuiston, A.R., Honke, K., Palavicini, J.P., Han, X., and Dupree, J.L. (2023) Adult-onset depletion of sulfatide leads to axonal degeneration with relative myelin sparing. Glia 71, 2285-2303. doi: 10.1002/glia.24423. PMCID: PMC11007682.
8. Palavicini, J.P., Din, L., Pan,, Qiu, S., Wang, H., Shen, Q., Dupree, J.L., and Han, X. (2022) Sulfatide deficiency, an early Alzheimer’s lipidomic signature, causes brain ventricular enlargement in the absence of classical neuropathological hallmarks. Int. J. Mol. Sci. 24, 233. PMCID: PMC9820719.
9. Qiu, S., Palavicini, J.P., Wang, J., Gonzalez, N.S., He, S., Dustin, E., Zou, C., Ding, L., Bhattacharjee, A., van Skike, C.E., Galvan, V., Dupree, J.L., and Han, X. (2021) Adult-onset CNS sulfatide deficiency is sufficient to cause Alzheimer’s disease-like neuroinflammation and cognitive impairment. Mol. Neurodegener. 16, 64. doi: 10.1186/s13024-021-00488-7. PMCID: PMC8442347.

https://scholars.uthscsa.edu/en/persons/xianlin-han