Isabella Xu
Program: Computational and Systems Biology
Current advisor: Jin-Moo Lee, MD, PhD
Undergraduate university: Washington University
Research summary
My research focuses on understanding how neuromodulation reshapes systemic immune responses after acute ischemic stroke. Ischemic stroke remains a leading cause of death and long-term disability, yet few therapies directly target the inflammatory responses that influence secondary injury, recovery, and post-stroke complications. Circulating monocytes are central mediators of this response, but the specific monocyte states and inflammatory programs that change after stroke in humans remain incompletely defined.
I study whether transcutaneous auricular vagus nerve stimulation (taVNS), a noninvasive strategy designed to engage vagal anti-inflammatory pathways, can modulate post-stroke immune activation. Using paired buffy coat samples collected before treatment and 72 hours after treatment from acute ischemic stroke patients randomized to taVNS or sham stimulation, we apply single-cell RNA sequencing and plasma proteomic profiling to define the cellular and molecular effects of vagal neuromodulation. Our preliminary analyses identified monocytes as the primary immune responders to taVNS and showed reduced inflammatory response and TNFα/NF-κB signaling in monocytes over the intervention period compared with sham-treated patients.
Building on these findings, my work aims to define the monocyte inflammatory states and regulatory programs altered by taVNS and determine whether these transcriptional changes are reflected in systemic protein signatures. By integrating single-cell transcriptomic and high-plex plasma proteomic data, we seek to identify immune pathways that explain taVNS-associated modulation of post-stroke inflammation. This work may help refine neuromodulatory strategies for immunomodulatory efficacy and nominate inflammatory pathways that could be targeted to improve recovery after stroke.
Graduate publications
Kim AB, Xiao Q, Yan P, Pan Q, Pandey G, Grathwohl S, Gonzales E, Xu I, Cho Y, Haecker H, Epelman S, Diwan A, Lee JM, DeSelm CJ. 2024 Chimeric antigen receptor macrophages target and resorb amyloid plaques. JCI Insight, 9(6):e175015.