Contact

  • Academic
    nnrl@stanford.edu
    University - Student Department: Bioengineering Position: Undergraduate
    University - Student Department: Aeronautics and Astronautics Position: Undergraduate
    University - Student Department: Department of Biomedical Data Science Position: Graduate

All Publications

  • Immunotherapy-related cognitive impairment after CAR T cell therapy in mice. Cell Geraghty, A. C., Acosta-Alvarez, L., Rotiroti, M. C., Dutton, S., O'Dea, M. R., Kim, W., Trivedi, V., Mancusi, R., Shamardani, K., Malacon, K., Woo, P. J., Martinez-Velez, N., Pham, T., Reche-Ley, N. N., Otubu, G., Castenada, E. H., Nwangwu, K., Xu, H., Mulinyawe, S. B., Zamler, D. B., Ni, L., Cross, K., Rustenhoven, J., Kipnis, J., Liddelow, S. A., Mackall, C. L., Majzner, R. G., Monje, M. 2025

    Abstract

    Immunotherapies have revolutionized cancer care for many tumor types, but their potential long-term cognitive impacts are incompletely understood. Here, we demonstrated in mouse models that chimeric antigen receptor (CAR) T cell therapy for both central nervous system (CNS) and non-CNS cancers impaired cognitive function and induced a persistent CNS immune response characterized by white matter microglial reactivity, microglial chemokine expression, and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis were disrupted. Single-nucleus sequencing studies of human frontal lobe from patients with or without previous CAR T cell therapy for brainstem tumors confirmed reactive states of microglia and oligodendrocytes following treatment. In mice, transient microglial depletion or CCR3 chemokine receptor blockade rescued oligodendroglial deficits and cognitive performance in a behavioral test of attention and short-term memory function following CAR T cell therapy. Taken together, these findings illustrate targetable neural-immune mechanisms underlying immunotherapy-related cognitive impairment.

    View details for DOI 10.1016/j.cell.2025.03.041

    View details for PubMedID 40359942

  • Oncogenic role of a developmentally regulated<i> NTRK2</i> splice variant SCIENCE ADVANCES Pattwell, S. S., Arora, S., Nuechterlein, N., Zager, M., Loeb, K. R., Cimino, P. J., Holland, N. C., Reche-Ley, N., Bolouri, H., Bonnin, D., Szulzewsky, F., V. Phadnis, V., Ozawa, T., Wagner, M. J., Haffner, M. C., Cao, J., Shendure, J., Holland, E. C. 2022; 8 (40): eabo6789

    Abstract

    Temporally regulated alternative splicing choices are vital for proper development, yet the wrong splice choice may be detrimental. Here, we highlight a previously unidentified role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in humans and mice. TrkB.T1 is the predominant NTRK2 isoform across embryonic organogenesis, and forced overexpression of this embryonic pattern causes multiple solid and nonsolid tumors in mice in the context of tumor suppressor loss. TrkB.T1 also emerges as the predominant NTRK isoform expressed in a wide range of adult and pediatric tumors, including those harboring tropomyosin receptor kinase fusions. Affinity purification-mass spectrometry proteomic analysis reveals distinct interactors with known developmental and oncogenic signaling pathways such as Wnt, transforming growth factor-β, Sonic Hedgehog, and Ras. From alterations in splicing factors to changes in gene expression, the discovery of isoform specific oncogenes with embryonic ancestry has the potential to shape the way we think about developmental systems and oncology.

    View details for DOI 10.1126/sciadv.abo6789

    View details for Web of Science ID 000886057300011

    View details for PubMedID 36206341

    View details for PubMedCentralID PMC9544329