Linking metabolic signal with gene expression:

Allosteric regulation of transcription factors by metabolites

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Paradoxical Activation of Oncofusions to Eliminate Cancer Cells

Growing evidence suggests that cancer cells can tolerate only a confined window of oncogenic signaling flux, and further activation of an already-activated oncogenic signaling pathway selectively impairs cell fitness. Our recent findings demonstrated that hyperactive EWS/FLI1, with enhanced chromatin occupancy induced by the loss of the transcription repressor ETV6, specifically inhibits Ewing sarcomagenesis. This sparks a new targeting strategy: enhancing the activity of oncofusions to selectively target cancers driven by these pathways. This approach will redefine 'druggability' in target discovery and inspire a new wave of drug development and repurposing against cancer.

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Selected Publications

  • Gao, Y., He XY., Wu, X., Huang Y., Toneyan S., Ipsaro, J., Ha, T., Koo, P., Joshua-Tor, L., Bailey, K., Egeblad, M., Vakoc, C.# “ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation.” Nature Cell Biology (2023)

        Featured as the Cover Story for Feb issue at Nat Cell Biol

        Highlighted by Prof. Elizabeth R Lawlor at Nature Cell Biology

  • He XY, Gao, Y., Ng D., Michalopoulou E., George S., Adrover JM., Sun L., Albrengues J., Daßler-Plenker J., Han X., Wan L., Wu XS., Shui LS., Huang YH., Liu B., Su C., Spector DL., Vakoc CR., Aelst LV., Egeblad M.# “Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment.” Cancer Cell (2024)

  • Wen, Q.*, Zhou, J.*, Tian, C.*, Li, X.*, Song, G.*, Gao, Y., …, Gan, H.# “Symmetric inheritance of parental histones safeguards the fate of mouse embryonic stem cells during differentiation.” Nature Genetics(2024)

  • Tian, C.*, Zhou, J.*, Li, X.*, Gao, Y., Wen, Q., Kang, X., Wang, N., Yao, Y., Jiang, J., Song, G., Zhang, T., Hu, S., Liao, J., Yu, C., Wang, Z., Liu, X., Pei, X., Chan, K., Liu, Z. & Gan, H.# “Impaired histone inheritance promotes tumor progression.” Nature Communications (2023)

  • Gao, Y., Gan, H., Lou, Z., and Zhang, Z.# “Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation.” Proceedings of the National Academy of Sciences of the United States of America (2018)