Alexander Liu

Program: Immunology

Current advisor: Marco Colonna, MD

Undergraduate university: Case Western Reserve University, 2021

Enrollment year: 2022

Research summary
Development of Engineered Chimeric Antigen Receptor Astrocytes (CAR-A) as a Therapeutic Platform for Alzheimer’s Disease

Alzheimer’s disease (AD) is the leading cause of dementia and affects over 5 million individuals in the United States. Recent anti amyloid-β (Aβ) monoclonal antibodies demonstrate that amyloid removal can modify disease trajectory; however, their clinical application is limited by poor brain penetration, treatment-associated toxicities, and dependence on repeated administration. These limitations highlight the need for durable, mechanistically flexible strategies capable of sustained Aβ clearance within the central nervous system (CNS).
Chimeric antigen receptor (CAR) technology enables antigen-specific recognition coupled to engineered intracellular signaling modules that drive effector functions. While CAR-based approaches have transformed cancer immunotherapy, their application to neurodegeneration remains largely unexplored. Astrocytes are abundant, long-lived CNS-resident glial cells with intrinsic phagocytic capacity and are not replaced by peripheral immune cells, making them an attractive platform for durable CAR engineering. My research focuses on developing engineered CAR astrocytes combining anti-Aβ single-chain variable fragments (scFvs) with phagocytic signaling domains to promote sustained Aβ clearance, attenuate downstream neuronal pathology, and reshape glial responses in AD.

Graduate publications
Chen Y, Liu Y, Nguyen K, Wu J, Song S, Lin K, Rodrigues PF, Du S, Zhou C, Xiong K, Bosch M, Lin PB, Khantakova D, Wu S, Wu M, Yuede C, Holtzman DM, Colonna M. 2026 Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy. Science, 391(6789):eads3972. PMCID:

Rodrigues PF*, Wu S*, Trsan T, Panda SK, Fachi JL, Liu Y, Du S, de Oliveira S, Antonova AU, Khantakova D, Sudan R, Desai P, Diamond MS, Gilfillan S, Anderson SK, Cella M, Colonna M. 2025 Rorγt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens. Cell, 188(10):2720-2737.e22. PMCID: PMC12085292

Cao S, Nguyen KM, Ma K, Tan T, Yao X, Liu TC, Ayoub M, Devi J, Samaan S, Liu Y, Smith R, Silviera ML, Hunt SR, Wise PE, Mutch MG, Glasgow SC, Chapman WC Jr, Cowan ML, Ciorba MA, Colonna M, Deepak P, SPARC IBD Investigators. 2025 Revealing hyperactivated IFN-γ pathways in perianal fistulizing Crohn’s disease using single-cell and spatial multi-omics. J Clin Invest, 135(17):e193413. PMCID: PMC12404762

Lonardi S, Bianchetto-Aguilera FM, Monti M, Di Matteo A, Missale F, Picinoli S, Bugatti M, Benedetti M, Ferrari G, Cassatella MA, Moratto D, Zini S, Agostini V, Savoldi V, Lorenzi L, Chiarini M, Facchetti F, Wu S, Antonova AU, Liu YA, Cella M, Ghigna C, Colonna M, Vermi W. 2025 Mapping of RORγt+ dendritic cells in human tissues establishes their preferential niche in adult lymph nodes. Front Immunol, 16():1527499. PMCID: PMC12162286

Panda SK, Kim DH, Desai P, Wu S, Rodrigues PF, Sudan R, Liu Y, Jung H, Lee I, Gilfillan S, Cella M, Van Dyken SJ, Colonna M. 2025 SLC7A8 is essential for metabolic fitness and function of Th2 cells. J Exp Med, 232(2)::e20250439. PMCID:

Molgora M, Liu YA, Colonna M, Cella M. 2023 TREM2: A new player in the tumor microenvironment. Semin Immunol, 67():101739

Pfeifer CW, Walsh JT, Santeford A, Lin JB, Beatty WL, Terao R, Liu YA, Hase K, Ruzycki PA, Apte RS. 2023 Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy. Proc Natl Acad Sci USA, 120(45):e2308214120. PMCID: PMC10636339