In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer.

The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments.  

References

Guil, S., Soler, M., Portela, A., Carrère, J., Fonalleras, E., Gómez, A., Villanueva, A., & Esteller, M. (2012). Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19(7), 664–670. https://doi.org/10.1038/nsmb.2315

Vizoso, M., Ferreira, H. J., Lopez-Serra, P., Carmona, F. J., Martínez-Cardús, A., Girotti, M. R., Villanueva, A., Guil, S., Moutinho, C., Liz, J., Portela, A., Heyn, H., Moran, S., Vidal, A., Martinez-Iniesta, M., Manzano, J. L., Fernandez-Figueras, M. T., Elez, E., Muñoz-Couselo, E., … Esteller, M. (2015). Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, 21(7), 741–750. https://doi.org/10.1038/nm.3863

Agrelo, R., Cheng, W.-H., Setien, F., Ropero, S., Espada, J., Fraga, M. F., Herranz, M., Paz, M. F., Sanchez-Cespedes, M., Artiga, M. J., Guerrero, D., Castells, A., von Kobbe, C., Bohr, V. A., & Esteller, M. (2006). Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America, 103(23), 8822–8827. https://doi.org/10.1073/pnas.0600645103

Lopez-Serra, P., Marcilla, M., Villanueva, A., Ramos-Fernandez, A., Palau, A., Leal, L., Wahi, J. E., Setien-Baranda, F., Szczesna, K., Moutinho, C., Martinez-Cardus, A., Heyn, H., Sandoval, J., Puertas, S., Vidal, A., Sanjuan, X., Martinez-Balibrea, E., Viñals, F., Perales, J. C., … Esteller, M. (2014). A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nature Communications, 5, 3608. https://doi.org/10.1038/ncomms4608

Rosselló-Tortella, M., Llinàs-Arias, P., Sakaguchi, Y., Miyauchi, K., Davalos, V., Setien, F., Calleja-Cervantes, M. E., Piñeyro, D., Martínez-Gómez, J., Guil, S., Joshi, R., Villanueva, A., Suzuki, T., & Esteller, M. (2020). Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 117(34), 20785–20793. https://doi.org/10.1073/pnas.2003358117

Castro de Moura, M., Davalos, V., Planas-Serra, L., Alvarez-Errico, D., Arribas, C., Ruiz, M., Aguilera-Albesa, S., Troya, J., Valencia-Ramos, J., Vélez-Santamaria, V., Rodríguez-Palmero, A., Villar-Garcia, J., Horcajada, J. P., Albu, S., Casasnovas, C., Rull, A., Reverte, L., Dietl, B., Dalmau, D., … Esteller, M. (2021). Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine, 66, 103339. https://doi.org/10.1016/j.ebiom.2021.103339

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