Bio

Dr. Chen completed a Bachelor of Science (Honours) at the University of Sydney (NSW, Australia), with majors in Molecular Biology and Immunobiology. She graduated with the University Medal for her Honours research project where she investigated the novel role of DNA damage repair machinery on telomerase recruitment to telomeres. She then undertook her graduate studies at the Peter MacCallum Cancer Centre (The University of Melbourne, VIC, Australia) in the Beavis laboratory, where she developed a CRISPR knock-in strategy to engineer armored CAR T cells to express therapeutic payloads in a tumor-restricted manner. She joined the Porteus laboratory in the Department of Pediatrics at Stanford University in March 2025, where she is developing strategies to enhance gene-edited hematopoietic stem cell transplantation.

Stanford Advisors

Contact

  • Academic
    amandaxc@stanford.edu
    University - Scholar Department: Pediatrics Position: Postdoctoral Scholar

Additional Info

All Publications

  • High efficiency CRISPR knock-in demonstrates that TCF1 is insufficient to reverse T cell exhaustion. Nature communications de Menezes, M. N., Chen, A. X., Kulkarni, N., Sampurno, S., Saw, N. Y., Yap, K. M., Perez-Nunez, I., Roth, S., Deguit, C. D., Haugen, B., Ramsbottom, K. M., Munoz, I., Beavis, P. A., Parish, I. A. 2026

    Abstract

    CD8+ T cell exhaustion is a regulatory state triggered by chronic antigen stimulation in both cancer and persistent infection. The less differentiated stem-like sub-populations of exhausted T cells have been heavily studied given their importance to the efficacy of current immunotherapies. While the transcription factor TCF1 is both necessary and sufficient for formation and maintenance of these stem-like populations, it remains unclear whether TCF1 can actively de-differentiate more terminally exhausted subsets back into a stem-like state. To address this question, here we utilize and optimize a high efficiency CRISPR knock-in methodology, compatible with mouse in vivo exhaustion models, to engineer T cells that either constitutively over-express TCF1, or conditionally over-express TCF1 following differentiation of the cells into a CX3CR1+ intermediate-exhausted state. Strikingly, we find that only constitutive, and not conditional, TCF1 over-expression can increase the size of the stem-like T cell pool. Thus, while TCF1 can slow stem-like T cell differentiation, it is insufficient to revert more differentiated cells back into a stem-like state.

    View details for DOI 10.1038/s41467-026-69671-y

    View details for PubMedID 41702943

  • Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8<SUP>+</SUP> T cells in lymph nodes NATURE IMMUNOLOGY Lai, J., Chan, C., Armitage, J. D., Audsley, K. M., Huang, Y., Derrick, E. B., Carstensen, L. S., Scheffler, C. M., Jones, M. E., Sek, K., Principe, N., Kim, J. S., House, I. G., Chen, A. X. Y., Yap, K., Middelburg, J., Munoz, I., Nguyen, D., Tong, J., Hoang, T. X., Todd, K. L., Evrard, M., Chee, J., Mackay, L. K., Forrest, A. R. R., Parish, I. A., Bosco, A., Waithman, J., Beavis, P. A., Darcy, P. K. 2026

    Abstract

    Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (TPEX), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. Here we show that treatment with Fms-related tyrosine kinase 3 ligand (Flt3L) expands CD62L+SLAMF6+CD8+ T cells in the tumor through a mechanism that requires XCR1+ dendritic cells to traffic to the tumor-draining lymph node. The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8+ T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8+ T cells within tumors through a mechanism that is dependent on lymph node egress.

    View details for DOI 10.1038/s41590-026-02419-4

    View details for Web of Science ID 001685849900001

    View details for PubMedID 41667622

    View details for PubMedCentralID 4081656

  • Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery. Nature Chen, A. X., Yap, K. M., Kim, J. S., Sek, K., Huang, Y. K., Dunbar, P. A., Wiebking, V., Armitage, J. D., Munoz, I., Todd, K. L., Derrick, E. B., Nguyen, D., Tong, J., Chan, C. W., Hoang, T. X., Audsley, K. M., van Elsas, M. J., Middelburg, J., Lee, J. N., de Menezes, M. N., Cole, T. J., Li, J., Scheffler, C., Scott, A. M., Mackay, L. K., Waithman, J., Oliaro, J., Harrison, S. J., Parish, I. A., Lai, J., Porteus, M. H., House, I. G., Darcy, P. K., Beavis, P. A. 2025

    Abstract

    The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumours is limited by immunosuppression and antigen heterogeneity1-3. To overcome these barriers, 'armoured' CAR T cells, which secrete proinflammatory cytokines, have been developed4. However, their clinical application has been limited because of toxicity related to peripheral expression of the armouring transgene5. Here, we have developed a CRISPR knock-in strategy that leverages the regulatory mechanisms of endogenous genes to drive transgene expression in a tumour-localized manner. By screening endogenous genes with tumour-restricted expression, we have identified the NR4A2 and RGS16 promoters as promising candidates to support the delivery of cytokines such as IL-12 and IL-2 directly to the tumour site, leading to enhanced antitumour efficacy and long-term survival of mice in both syngeneic and xenogeneic models. This effect was concomitant with improved CAR T cell polyfunctionality, activation of endogenous antitumour immunity and a favourable safety profile, and was applicable in CAR T cells from patients.

    View details for DOI 10.1038/s41586-025-09212-7

    View details for PubMedID 40604285

    View details for PubMedCentralID 4433819

https://orcid.org/0000-0002-1388-9510