Dc. Estebanez Group

Molecular Structure of Nuclear Receptors

Dc. Eva Estébanez-Perpiñá

About Us
What Do We Research?
Publications

Contact:

email: cevaestebanez@ub.edu

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.

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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 – Universidad de Barcelona & NIH
  • Andrea Alegre-Martí, Predoctoral researcher
  • Montserrat Abella Monleón, Technician
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What Do We Research?

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.

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

  1. 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
    Sci Adv. 2023 Mar 17;9(11):eade2175
  2. 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 Res. 2022 Dec 9;50(22):13063-13082.
  3. 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
    2023 May 24 Online ahead of print.
  4. Nadal M, Prekovic S, Gallastegui N, et al, Claessens F, Fuentes-Prior P and Estébanez-Perpiñá E
    Nat Commun. 2017 Feb 6;8:14388.
  5. 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. 2022 Mar 29;119(13):e2023784119.
  6. Vahid Sheikhhassani, Barbara Scalvini, Julian Ng, Laurens Heling, Estébanez-Perpiñá E, Iain J. McEwan, Alireza Mashaghi
    Protein Sci. 2022 Jun;31(6):e4334.
  7. de Bosscher K, Desmet J, Estébanez-Perpiñá E, Brunsveld L
    Nat Rev Endocrinol. 2020 Jul;16(7):363-377
  8. Fuentes-Prior P, Rojas A, Hagler AT and Estébanez-Perpiñá E
    Trends Biochem Sci. 2019 Jan;44(1):2-6.
  9. Sevilla L, Pons O, Alegre A, Estébanez-Perpiñá E, Vitellius G, Pérez P
    FASEB J. 2023 Jan;37(1):e22709.
  10. 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.
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