Alexander Liu
Program: Immunology
Current advisor: Marco Colonna, MD
Undergraduate university: Case Western Reserve University
Research summary
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
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.