Structural Biology of Human Nuclear Receptors
Department of Biochemistry and molecular Biology
Faculty of Biology, UB
Eva Estébanez-Perpiñá
ORCID ID: 0000-0003-2687-5801
Tel +34 93 403 11 19
https://www.ub.edu/nurcamein/en/groups/doctor-estebanez-group/
Principal investigator: • Eva Estébanez-Perpiñá
PostDoc researcher: • Andrea Alegre-Martí • Alba Jiménez-Panizo
PhD students: • Inés Montoya-Novoa • José Luis Torbado-Gardeazábal
Lab Manager and Technician: • Montserrat Abella
Tel +34 93 403 11 19
https://www.ub.edu/nurcamein/en/groups/doctor-estebanez-group/
Principal investigator: • Eva Estébanez-Perpiñá
PostDoc researcher: • Andrea Alegre-Martí • Alba Jiménez-Panizo
PhD students: • Inés Montoya-Novoa • José Luis Torbado-Gardeazábal
Lab Manager and Technician: • Montserrat Abella
Current
Research
Current Research
Our laboratory studies several members of the superfamily of nuclear receptors (NRs), which are transcription factors that regulate gene expression. There are 48 nuclear receptors in humans, some of them have their endogenous ligand and functions well characterized, while others are regarded as orphans as their ligand or function is still not completely understood.
We primarily focus on the androgen receptor (AR), glucocorticoid receptor (GR) and human tailless (NR2E1/TLX) receptor. AR is implicated in prostate cancer, androgen insensitivity syndromes and the rare neurodegenerative Kennedy’s disease. AR is also the central drug target to fight prostate cancer using antiandrogens. GR is an essential receptor for life and binds glucocorticoids, one of the most important drug classes to treat immune diseases and inflammation (asthma, psoriasis, arthritis). We study GR oligomerization to further understand its monomer to dimer to tetramer transitions and pharmacological outcome of glucocorticoids. Lastly, we focus on TLX for its therapeutic potential as drug target to treat glioblastoma and meduloblastoma as well as modulation of brain neurogenesis.
Nuclear Receptors Structure and Function Relationship
We tackle the biological processes controlled by NRs from a multidisciplinary approach using several biochemical and biophysical techniques (X-ray crystallography, SPR, SAXS, MS) as well as in vitro and in cellulo to understand their function in tissues under (patho)-physiological conditions.
AR, GR and TLX in Drug Discovery
- We combine structure-based drug design, combinatorial chemistry, and bioinformatics to identify novel first-in-class AR precision drugs against prostate cancer and other AR-related diseases.
- Our studies on GR oligomerization focuses on the development of novel glucocorticoids devoid of severe side effects that modulate GR multimers on chromatin.
- Design of TLX modulators to tackle incurable brain tumors.
Selected
Publications
Andrea Alegre-Martí, Alba Jiménez-Panizo, Adrián Martínez-Tébar, Coralie Poulard, M Núria Peralta-Moreno, Montserrat Abella, Rosa Antón, Marcos Chiñas, Ulrich Eckhard, Josep M Piulats, Ana M Rojas, Juan Fernández-Recio, Jaime Rubio-Martínez, Muriel Le Romancer, Álvaro Aytes, Pablo Fuentes-Prior, Eva Estébanez-Perpiñá. A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance. Sci. Adv.9,eade2175(2023). DOI:10.1126/sciadv.ade2175
Jiménez-Panizo, A.; Alegre-Martí, A.; Tettey, T. T.; Fettweis, G.; Abella, M.; Antón, R.; Johnson, T. A.; Kim, S.; Schiltz, R. L.; Núñez-Barrios, I.; Font-Díaz, J.; Caelles, C.; Valledor, A. F.; Pérez, P.; Rojas, A. M.; Fernández-Recio, J.; Presman, D. M.; Hager, G. L.; Fuentes-Prior, P.; Estébanez-Perpiñá, E. The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities. Nucleic Acids Research. gkac1119, 2022 doi.org/10.1093/nar/gkac1119
Nadal, M.; Prekovic, S.; Gallastegui, N.; Helsen, C.; Abella, M.; Zielinska, K.; Gay, M.; Vilaseca, M.; Taulès, M.; Houtsmuller, A. B.; van Royen, M. E.; Claessens, F.; Fuentes-Prior, P.; Estébanez-Perpiñá, E. Structure of the homodimeric androgen receptor ligand-binding domain. Nature Communications. 2017 Feb 6;8:14388, 2017. doi.org/10.1038/ncomms14388
Kandel, P.; Semerci, F.; Mishra, R.; Choi, W.; Bajic, A.; Baluya, D.; Ma, L.; Chen, K.; Cao, A. C.; Phongmekhin, T.; Matinyan, N.; Jiménez-Panizo, A.; Chamakuri, S.; Raji, I. O.; Chang, L.; Fuentes-Prior, P.; MacKenzie, K. R.; Benn, C. L.; Estébanez-Perpiñá, E.; Venken, K.; Moore, D. D.; Young, D. W.; Maletic-Savatic, M. Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis.Proceedings of the National Acadademy of Sciences. 119(13): e2023784119, 2022. doi.org/10.1073/pnas.2023784119
Ana Paredes, Raquel Justo-Méndez, Daniel Jiménez-Blasco, Vanessa Núñez, Irene Calero, María Villalba-Orero, Andrea Alegre-Martí, Thierry Fischer, Ana Gradillas, Viviane Aparecida Rodrigues Sant’Anna, Felipe Were, Zhiqiang Huang, Pablo Hernansanz-Agustín, Carmen Contreras, Fernando Martínez, Emilio Camafeita, Jesús Vázquez, Jesús Ruiz-Cabello, Estela Area-Gómez, Fátima Sánchez-Cabo, Eckardt Treuter, Juan Pedro Bolaños, Eva Estébanez-Perpiñá, Francisco Javier Rupérez, Coral Barbas, José Antonio Enríquez, Mercedes Ricote. Nature https://doi-org.sire.ub.edu/10.1038/s41586-023-06068-7
Selected
Publications
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Author
P. Fuentes-Prior, A. Rojas, AT Hagler, E. Estébanez-PerpiñáIdentification
2018 Oct 4, in press