Huixin Xu

Assistant Professor, Neurobiology and Behavior
Charlie Dunlop School of Biological Sciences

Choroid plexus, cerebrospinal fluid, brain barrier, neuroimmune, aging, Alzheimer's disease

faculty.sites.uci.edu/huixinxulab/

We study the brain from its fluids and barriers. Specifically, we seek to understand how cerebrospinal fluid (CSF) and the choroid plexus shape the brain microenvironment in brain aging and neurodegenerative disorders like Alzheimer’s disease. CSF bathes the entire central nervous system, providing a rich menu of active factors for brain cells and promptly removing their wastes. Most of CSF is produced by the choroid plexus, a secretory epithelial tissue that also forms the blood-CSF barrier to selectively gate the entry of not only blood-borne molecules, but also peripheral immune cells, into the brain. We use longitudinal in vivo imaging approach combined with neuroimmunology and multi-omics tools in rodent models and human tissues to answer the pressing questions: how do brain aging and Alzheimer’s disease drive choroid plexus dysfunction? How does choroid plexus dysfunction harms brain microenvironment and accelerate neurodegeneration? Can we reverse or supplement for the deficits by taking advantage of the choroid plexus and its exceptional ability to secrete factors? Together, we aim to discover mechanisms to fine-tune brain microenvironment and inspire new therapies.

I received my B.S. in Chemistry and Biology from Tsinghua University. I completed my PhD training at Harvard University, studying Alzheimer’s disease with Dr. Dennis Selkoe. I then completed her postdoctoral training at Boston Children’s Hospital with Dr. Maria Lehtinen, where I discovered that the choroid plexus actively conducts immune infiltration into the brain during acute brain inflammation and modulates its own barrier integrity accordingly. I also studied hydrocephalus and CSF water and ion regulation by the choroid plexus during brain development and following brain bleeding. Towards the end of my postdoctoral training, I was awarded a BrightFocus postdoctoral fellowship which enabled me to pursue a project combining my expertise in the choroid plexus – CSF system with my enthusiasm in Alzheimer’s disease, which then led to the opening of my lab.

Huixin Xu*, Peter Lotfy*, Benjamin Englert#, Jane Oberhauser#, Lillian I.J. Byer, Jasmin Wihlman, Kia Colangelo, Serhat V. Okar, Ashley Thommana, Henri Puttonen, Mikko I. Mäyränpää, Jarno Tuimala, Rute Pedrosa, Darshan Kumar, James Francis Haberberger, Micaiah Emmy Atkins, Shon Alimukhamedov, Aja Pragana, Jordan Benson, Mary Elizabeth Gabrielle, Anna Dong, Violeta Durán Laforet, Peter Bor-Chian Lin, C. Dirk Keene, Caitlin S. Latimer, Katherine E. Prater, David M. Holtzman, Alina Isakova, Tony Wyss-Coray, Dorothy P. Schafer, Daniel S. Reich, Terho Lehtimäki, Pekka J. Karhunen, Eloise H. Kok, Deidre Jansson, Andrew C. Yang†, Liisa Myllykangas†, Jose Ordovas-Montanes†, Maria K. Lehtinen†. Multi-modal choroid plexus pathology in aging and Alzheimer’s disease. bioRxiv. 2025. (* # † these authors contributed equally)

Huixin Xu, Christine Hehnly, Maria K. Lehtinen. The choroid plexus: A command center for brain-body communication during inflammation. Current Opinion in Immunology. 2025 Apr;93:102540. PMID: 40020255

Lillian I. J. Byer, Huixin Xu, Maria K. Lehtinen. Protocol for the dissection, immunostaining, and imaging of whole-mount mouse choroid plexus. STAR Protocols, 2025 Feb 27;6(1):103627. PMID: 40019836.

Huixin Xu, Peter Lotfy, Sivan Gelb, Aja Pragana, Christine Hehnly, Lillian I. J. Byer, Frederick B. Shipley, Miriam E. Zawadzki, Jin Cui, Liwen Deng, Milo Taylor, Mya Webb, Hart G. Lidov, Mark L. Andermann, Isaac M. Chiu, Jose Ordovas-Montanes, Maria K. Lehtinen. The choroid plexus synergizes with immune cells during neuroinflammation. Cell, 2024 Sep 5; 187(18), 4946-4963.e4917. doi: 10.1016/j.cell.2024.07.002. PMID: 39089253.

Meredith Skiba, Sarah Sterling, Shaun Rawson, Shuhao Zhang, Huixin Xu, Haoran Jiang, Genevieve R. Nemeth, Morgan S.A. Gilman, Joseph D. Hurley, Pengxiang Shen, Dean P. Staus, Jihee Kim, Conor McMahon, Maria K. Lehtinen, Howard A. Rockman, Patrick Barth, Laura M. Wingler, Andrew C. Kruse. Antibodies Expand the Scope of Angiotensin Receptor Pharmacology. Nature Chemical Biology, Nat Chem Biol. 2024;20(12):1577-1585. doi:10.1038/s41589-024-01620-6. PMID: 38744986

Huixin Xu, Guillaume P. Dugué, Yasmine Cantaut-Belarif, Suhasini Gupta, Claire Wyart, Maria K. Lehtinen. SCO-spondin knockout in mice leads to small brain ventricles and mild spine deformation. Fluids and Barriers of the CNS, 2023 Dec 5;20(1):89. doi: 10.1186/s12987-023-00491-8. PMID: 38049798

Ryann M Fame, Peter N. Kalugin, Boryana Petrova, Huixin Xu, Paul A Soden, Frederick B. Shipley, Neil Dani, Bradford Grant, Aja Pragana, Joshua P. Head, Suhasini Gupta, Morgan L. Shannon, Fortunate F. Chifamba, Hannah Hawks-Mayer, Amanda Vernon, Fan Gao, Yong Zhang, Michael J. Holtzman, Myriam Heiman, Mark L. Andermann, Naama Kanarek, Jonathan O. Lipton, Maria K. Lehtinen. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nature Communications, 2023 Jun 22;14(1):3720. PMID: 37349305

Ryann M. Fame*, Huixin Xu*, Aja Pragana, Maria Lehtinen, Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1. Fluids Barriers CNS, 2023 Jun 16;20(1):45. PMID: 37328833 (*co-first authors).

Cameron Sadegh*, Huixin Xu*, Jason Sutin, Benoit Fatou, Suhasini Gupta, Aja Pragana, Milo Taylor, Peter N. Kalugin, Miriam E. Zawadzki, Osama Alturkistani, Frederick B. Shipley, Neil Dani, Ryann M. Fame, Zainab Wurie, Pratik Talati, Riana L. Schleicher, Eric M. Klein, Yong Zhang, Michael J. Holtzman, Christopher I. Moore, Pei-Yi Lin, Aman B. Patel, Benjamin C. Warf, W. Taylor Kimberly, Hanno Steen, Mark L. Andermann, Maria K. Lehtinen. Choroid plexus targeted NKCC1 overexpression for the treatment of post-hemorrhagic hydrocephalus. Neuron, 2023 May 17;111(10):1591-1608. PMID: 36893755 (*co-first authors).

Jin Cui*, Huixin Xu*, Maria Lehtinen. Macrophages on the margin. Trends in Neurosciences, 2021 Jul 23:S0166-2236(21)00124-7. PMID: 34312005 (Review; *co-first authors)

Huixin Xu*, Ryann M. Fame*, Cameron Sadegh, Jason Sutin, Christopher Naranjo, Della Syau, Jin Cui, Frederick B. Shipley, Amanda Vernon, Fan Gao, Yong Zhang, Michael J. Holtzman, Myriam Heiman, Benjamin C. Warf, Pei-Yi Lin, Maria K. Lehtinen. Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development. Nature Communications, 2021 Jan 19;12(1):447. PMID: 33469018. (*co-first authors)

Frederick B. Shipley*, Neil Dani*, Huixin Xu, Christopher Deister, Jin Cui, Joshua P. Head, Cameron Sadegh, Ryann M. Fame, Morgan L. Shannon, Vanessa I. Flores, Thomas Kishkovich, Emily Jang, Eric M. Klein, Glenn J. Goldey, Kangmin He, Yong Zhang, Michael J. Holtzman, Tomas Kirchhausen, Claire Wyart, Christopher I. Moore, Mark L. Andermann, Maria K. Lehtinen. Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface. Neuron, 2020 Nov 25;108(4):623-639.e10. PMID: 32961128 (*equal contribution)

Huixin Xu, Maria K. Lehtinen. Choroid Plexus Organoids: Harnessing CSF Gatekeepers for Brain Therapeutics. Cell Stem Cell, 2020 Aug 6;27(2):191-192. PMID: 32763178. (Preview)

Huixin Xu, Maria K. Lehtinen. Cerebrospinal Fluid Magnetic Resonance Imaging: Improving Early Diagnosis of Autism and Other Neurodevelopmental Conditions. Biological Psychiatry Cognitive Neuroscience and Neuroimaging, 2020 Jul;5(7):635-637. PMID: 32646616. (Comment)

Huixin Xu, Molly M. Rajsombath, Pia Weikop, Dennis J. Selkoe. Enriched environment enhances ß-adrenergic signaling to prevent microglia inflammation by amyloid-ß. EMBO Molecular Medicine, 2018 Sep;10(9):e8931. PMID: 30093491.

Amanda Lancer, Rafael M. Rezende, Stephen Rubino, Paul J. Lorello, Dustin J. Donnelly, Huixin Xu, Lauren A. Lau, Chris G. Dulla, Barbara J. Caldarone, Simon C. Robson, Howard L. Weiner. Seizure phenotype and ATP/Adenosine imbalance in the cerebrospinal fluid of CD39-/- mice. Immunology, 2017 Jul; 152(4):589-601. PMID: 28742222.

Ting Yang, Shaomin Li, Huixin Xu, Dominic M. Walsh and Dennis J. Selkoe. Large Soluble Oligomers of Amyloid ß-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate. Journal of Neuroscience, 2017 Jan 4;37 (1) 152-163. PMID: 28053038

Huixin Xu, Eilrayna Gelyana, Molly Rajsombath, Ting Yang, Shaomin Li, Dennis J. Selkoe. Environmental enrichment potently prevents microglia-mediated neuroinflammation by human amyloid ß-protein oligomers. Journal of Neuroscience, 2016 Aug 31;36(35):9041-56. PMID: 27581448.

Ming Lei, Huixin Xu, Zhangyuan Li, Zemin Wang, Tiernan T. O'Malley, Dainan Zhang, Dominic M.Walsh, Pingyi Xu, Dennis J. Selkoe, Shaomin Li. Soluble Aß oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance. Neurobiology of Disease, 2016 Jan;85:111-21. PMID: 26525100.

Interdepartmental Neuroscience Program

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https://faculty.uci.edu/profile/?facultyId=7368

Last updated
04/14/2026