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Dc. Estebanez Group

Molecular Structure of Nuclear Receptors

Dc. Eva Estébanez-Perpiñá

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Eva Estébanez-Perpiñá has a PhD in Biochemistry from the Max-Planck-Institute fuer Biochemie (MPI) and the Autonomous University of Barcelona, under the supervision of Nobel Prize Laureate Robert Huber and Wolfram Bode. In 2009, after her postdoctoral training in the group of Robert J. Fletterick in collaboration with John D. Baxter in UCSF (San Francisco, California, she joined the Institute of Biomedicine of the University of Barcelona (IBUB) and the Department of Biochemistry and Molecular Biomedicine at the School of Biology from the University of Barcelona as a research group leader. Her research is focused on the structural and molecular determinants responsible for nuclear receptors functions such as ligand binding, coregulators recognition, and their physiopathological actions in prostate cancer and brain tumors. Her work has demonstrated the relevance of developing allosteric modulators of nuclear receptors, having identified the first druggable allosteric pockets on these transcription factors as well as having resolved first crystal structures of non-canonical dimers of the androgen, glucocorticoid and thyroid receptors.

About Us

Eva Estébanez-Perpiñá, PhD Profesora Agregada Serra Húnter – Universidad de Barcelona

Pablo Fuentes-Prior, PhD Research Associate

Alba Jiménez-Paniño, PhD, Postdoctoral Fellow IDIBELL – UB

Andrea Alegre-Martí, PhD, Postdoctoral Fellow IDIBELL – UB

Inés Montoya-Novoa, Predoctoral fellow

José Luis Torbado-Gardeazábal, Predoctoral FPI fellow

Iain Visa-Ceccaroni, Predoctoral FI-STEP fellow

Pilar Montanyà-Vallugera, TFM student

Josep Ponsetí-Pons, TFM student

Montserrat Abella Monleón, Technician

What Do We Research?

Structure-function Relationship in Nuclear Receptor

The laboratory studies several members of the superfamily of nuclear receptors by means of several biochemical and biophysical techniques such as X-ray crystallography and surface plasmon resonance (SPR). 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.

Current Research Lines

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 such as spinal and bulbar muscular atrophy or androgen insensitivity syndromes. Our studies on GR or AR oligomerization focuses on the development of novel glucocorticoids or antiandrogens devoid of severe side effects that modulate GR or AR multimers on chromatin. We also design TLX modulators to tackle incurable brain tumors such as glioblastoma multiforme.

Publications

Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers
AGregory Fettweis, Kaustubh Wagh, Diana A Stavreva, Alba Jiménez-Panizo, Sohyoung Kim, Michelle Lion, Andrea Alegre-Martí, Lorenzo Rinaldi, Thomas A Johnson, Elise Gilson, Manan Krishnamurthy, Li Wang, David A Ball, Tatiana S Karpova, Arpita Upadhyaya, Didier Vertommen, Juan Fernández Recio, Eva Estébanez-Perpiñá, Franck Dequiedt, Gordon L Hager
Nucleic Acids Research (NAR), Volume 53, Issue 9, 22 May 2025, gkaf415,
The multimerization pathway of the glucocorticoid receptor
Andrea Alegre-Martí, Alba Jiménez-Panizo, Agustina L Lafuente, Thomas A Johnson, Inés Montoya-Novoa, M Nuria Peralta-Moreno, Pilar Montanyà-Valluguera, Josep Ponsetí-Pons, Montserrat Abella, Sohyoung Kim, Mireia Díaz, Marta Vilaseca, Paloma Pérez, Juan Fernández-Recio, Jaime Rubio-Martínez, Diego M Presman, Gordon L Hager, Pablo Fuentes-Prior, Eva Estébanez-Perpiñá
Nucleic Acids Research (NAR), Volume 53, Issue 19, 28 October 2025, gkaf1003,
A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance
Alegre-Martí A, Jiménez-Panizo A, Martínez-Tébar A, Poulard C, Peralta-Moreno MN, Abella M, Antón R, Chiñas M, Eckhard U, Piulats JM, Rojas AM, Fernández-Recio J, Rubio-Martínez J, Le Romancer M, Aytes Á, Fuentes-Prior P, Estébanez-Perpiñá E
Science Advances. 2023 Mar 17;9(11):eade2175
The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities
Jiménez-Panizo A, Alegre-Martí A, Fettweis G, Abella M, Antón R, Tettey T, Schiltz RL, Johnson TA, Nuñez-Barrios I, Font-Díaz J, Caelles C, Valledor AF, Pérez P, Rojas AM, Fernández-Recio J, Presman DM, Hager GL, Fuentes-Prior P, Estébanez-Perpiñá E
Nucleic Acids Research (NAR). 2022 Dec 9;50(22):13063-13082.
γ-Linolenic acid in maternal milk drives cardiac metabolic maturation. Nature
Paredes A, Justo-Méndez R, Jiménez-Blasco D, Núñez V, Calero I, Villalba-Orero M, Alegre-Martí A, Fischer T, Gradillas A, Rodrigues Sant’Anna VA, Were F, Huang Z, Hernansanz-Agustín P, Contreras C, Martínez F, Camafeita E, Vázquez J, Ruiz-Cabello J, Area-Gómez E, Sánchez-Cabo F, Treuter E, Bolaños JP, Estébanez-Perpiñá E, Rupérez FJ, Barbas C, Enríquez JA, Ricote M
Nature, 2023 Jul;619(7968):E24.
Structure of the homodimeric androgen receptor ligand-binding domain
Nadal M, Prekovic S, Gallastegui N, et al, Claessens F, Fuentes-Prior P and Estébanez-Perpiñá E
Nature Communications. 2017 Feb 6;8:14388.
Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis
Kandel P, Semerci F, Mishra R, Choi W, Bajic A, Baluya D, Ma L, Chen K, Cao AC, Phongmekhin T, Matinyan N, Jiménez-Panizo A, Chamakuri S, Raji IO, Chang L, Fuentes-Prior P, MacKenzie KR, Benn CL, Estébanez-Perpiñá E, Venken K, Moore DD, Young DW, Maletic-Savatic M
Proc Natl Acad Sci U S A (PNAS). 2022 Mar 29;119(13):e2023784119.
Diversity of Quaternary Structures Regulates Nuclear Receptor Activities
Fuentes-Prior P, Rojas A, Hagler AT and Estébanez-Perpiñá E
Trends Biochem Sci (TiBS). 2019 Jan;44(1):2-6.
The mineralocorticoid receptor modulates timing and location of genomic binding by glucocorticoid receptor in response to synthetic glucocorticoids in keratinocytes
Sevilla L, Pons O, Alegre A, Estébanez-Perpiñá E, Vitellius G, Pérez P
FASEB J. 2023 Jan;37(1):e22709.
Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development
Font-Díaz J, Jiménez-Panizo A, Caelles C, Vivanco MD, Pérez P, Aranda A, Estébanez-Perpiñá E, Castrillo A, Ricote M, Valledor AF
Semin Cancer Biol. 2021 Aug;73:58-75.