Stanford Medicine News Center Topics Awards & Honors January Recognitions Laura Attardi, PhD

Laura Attardi, PhD

Attardi has been named a fellow of the American Association for Cancer Research Academy. The Catharine and Howard Avery Professor in the School of Medicine and professor of genetics and of radiation oncology is being honored for her research dedicated to delineating p53 transcriptional networks, identifying novel p53 target genes critical for tumor suppression, and characterizing mechanisms by which p53 governs cell fate.

Laura Attardi
Catharine and Howard Avery Professor of the School of Medicine and Professor of Genetics

Publications

  • p53 promotes revival stem cells in the regenerating intestine after severe radiation injury. Nature communications Morral, C., Ayyaz, A., Kuo, H. C., Fink, M., Verginadis, I. I., Daniel, A. R., Burner, D. N., Driver, L. M., Satow, S., Hasapis, S., Ghinnagow, R., Luo, L., Ma, Y., Attardi, L. D., Koumenis, C., Minn, A. J., Wrana, J. L., Lee, C. L., Kirsch, D. G. 2024; 15 (1): 3018

    Abstract

    Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.

    View details for DOI 10.1038/s41467-024-47124-8

    View details for PubMedID 38589357

    View details for PubMedCentralID 8082264

  • Epigenetic priming targets tumor heterogeneity to shift transcriptomic phenotype of pancreatic ductal adenocarcinoma towards a Vitamin D susceptible state. Cell death & disease He, B., Stoffel, L., He, C. J., Cho, K., Li, A. M., Jiang, H., Flowers, B. M., Nguyen, K. T., Wang, K. W., Zhao, A. Y., Zhou, M. N., Ferreira, S., Attardi, L. D., Ye, J. 2024; 15 (1): 89

    Abstract

    As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state. Increasing overall H3K27 acetylation with GTA and reducing overall DNA methylation with 5-Aza not only elevated the Vitamin D receptor (VDR) expression but also reprogrammed the Vitamin D-responsive genes. Consequently, Vitamin D inhibited cell viability and migration in the epigenetically primed PDAC cells by activating genes involved in apoptosis as well as genes involved in negative regulation of cell proliferation and migration, while the opposite effect of Vitamin D was observed in unprimed cells. Studies in genetically engineered mouse PDAC cells further validated the effects of epigenetic priming for enhancing the anti-tumor activity of Vitamin D. Using gain- and loss-of-function experiments, we further demonstrated that VDR expression was necessary but not sufficient for activating the favorable transcriptomic phenotype in respond to Vitamin D treatment in PDAC, highlighting that both the VDR and Vitamin D-responsive genes were prerequisites for Vitamin D response. These data reveal a previously undefined mechanism in which epigenetic state orchestrates the expression of both VDR and Vitamin D-responsive genes and determines the therapeutic response to Vitamin D in PDAC.

    View details for DOI 10.1038/s41419-024-06460-9

    View details for PubMedID 38272889

    View details for PubMedCentralID 5858034

  • Targeting p53 gain-of-function activity in cancer therapy: a cautionary tale. Cell death and differentiation Attardi, L. D., Boutelle, A. M. 2023

    View details for DOI 10.1038/s41418-023-01253-7

    View details for PubMedID 38151545

    View details for PubMedCentralID 7954925

  • NF1 MUTATION IN OLIGODENDROCYTE PRECURSOR CELLS INDUCES PRENEOPLASTIC LESIONS IN THE BRAIN Pan, Y., Hysinger, J., Yalcin, B., Lennon, J., Raghavan, P., Schindler, N., Anastasaki, C., Chatterjee, J., Mount, C., Nagaraja, S., Scheaffer, S., Attardi, L., Gutmann, D., Monje, M. OXFORD UNIV PRESS INC. 2023

    View details for Web of Science ID 001115245401369

  • Tissue-regeneration program underlies lung-cancer suppression NATURE Attardi, L. D., Kaiser, A. M. 2023

    View details for DOI 10.1038/d41586-023-02025-6

    View details for Web of Science ID 001038056400005

    View details for PubMedID 37468810

    View details for PubMedCentralID 5659188

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