PROJECT
SUPERVISORS

Project Supervisor

Esteban Ballestar

Background

I started my scientific career by studying Biochemistry and Molecular Biology at the University of Valencia in Spain. I gained my first research experience during a number of internships at different departments of my university. Back then, I became excited about how cells pack the DNA and manage the information through chromatin and joined the team of Luis Franco for my PhD thesis. Later, I joined Alan Wolffe's team at the National Institutes of Health (Bethesda, USA) where I investigated the association between histone modifiers and methylated DNA.

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After this period, I worked at the Spanish National Cancer Center (CNIO), in association with Manel Esteller's group, where I shifted my research to cancer epigenetics. At that time, I realized that, while the field of cancer epigenetics was booming, there was little progress in epigenetics in relation to immune pathological conditions. In 2008, I became group leader at the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona where my research focused on epigenetic mechanisms in immune cells. During this period, my team showed the relevance of epigenetic dysregulation in major immune-mediated diseases and investigated mechanisms underlying the acquisition of targeted epigenetic changes in immune cells. In 2019, I moved my team to the Josep Carreras Leukaemia Research Institute (IJC), where we continue working on these topics.

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Research

As a group, we are fascinated about how immune cells acquire a high diversity of functions in association with vast changes in their epigenetic profiles. We want to know how epigenetic regulation is related to immune cell function and the mechanisms that participate in the establishment of epigenetic profiles in immune cells, and how the genetic information is used and interpreted.

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In addition, we also want to understand how epigenetic profiles in immune cells become altered in different immune-mediated diseases, particularly in autoimmune diseases and in primary immunodeficiencies. This is important in conditions with defined mutations, in others that depend on the contributions of many different genetic variants and in those in which the genetic contribution remains elusive. We believe that a better understanding of what happens in these diseases will allow us to find interventions and improve current therapies.

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Publications

Morante-Palacios, O., Godoy-Tena, G., Calafell-Segura, J., Ciudad, L., Martínez-Cáceres, E., Sardina, J.L., Ballestar, E. (2022) Vitamin C enhances NF-kB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells. Nucleic Acids Research 50, 10981–10994.

Rodríguez-Ubreva, J., Arutyunyan, A., Bonder, M.J., Del Pino-Molina, L., Clark, S.J., de la Calle-Fabregat, C., Garcia-Alonso, L., Handfield, L.-F., Ciudad, L., Andrés-León, E., Krueger, F., Català-Moll, F., Rodríguez-Cortez, V.C., Polanski, K. Mamanova, L. van Dongen, S., Kiselev, V.Yu. Martínez-Saavedra, M.T., Heyn, H., Martín, J. Warnatz, K., López-Granados, E., Rodríguez-Gallego, C., Stegle, O., Kelsey, G., Vento-Tormo, R., and Ballestar, E. (2022) Single-Cell Atlas of Common Variable Immunodeficiency reveals germinal center-associated epigenetic dysregulation in B cell responses. Nature Communications 13,1779.

de la Calle-Fabregat, C., Rodríguez-Ubreva, J., Ciudad, L., Ramírez, J., Celis, R., Azuaga, A.B., Cuervo, A., Graell, E., Pérez-García, C., Díaz-Torné, C., Salvador, G., Gómez-Puerta, J.A., Haro, I., Sanmartí, R., Cañete, J.D., and Ballestar, E. (2022) The synovial and blood monocyte DNA methylomes mirror prognosis, evolution and treatment in early arthritis. JCI Insight 7, e158783.

Català-Moll, F., Ferreté-Bonastre, A.G., Li, T., Weichenhan, D., Lutsik, P., Ciudad, L., Álvarez-Prado, Á., Rodríguez-Ubreva, J., Klemann, C., Speckmann, C., Vilas-Zornoza, A., Abolhassani, H., Martínez-Gallo, M., Dieli-Crimi, R., Rivière, J., Martín-Nalda, A., Colobran, R., Soler-Palacín, P., Kracker, S., Hammarström, L., Prosper, F., Durandy, A., Grimbacher, B., Plass, C., and Ballestar, E. (2021) Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction. Nucleic Acids Research 49, 5057–5073

Garcia-Gomez, A., Li, T., de la Calle-Fabregat, C., Rodríguez-Ubreva, J., Ciudad, L., Català-Moll, F., Godoy-Tena, G., Martín-Sánchez, M., San-Segundo, L., Muntión, S., Morales, X., Ortiz de Solórzano, C., Oyarzabal, J., San-José Enériz, E., Esteller, M., Agirre, X., Prosper, F., Garayoa, M. and Ballestar, E. (2021) Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease. Nature Communications 12, 421.