Our Research

Our laboratory studies several members of the family of nuclear receptors (NRs) that regulate gene expression in many tissues. There are 48 nuclear receptors in humans, some of them have their ligand and functions well-characterized, while others are regarded as orphans as their ligand or function is still not completely described. Among the steroid subclass of NRs, we study the androgen receptor (AR), which is implicated in prostate cancer, androgen insensitivity syndromes and the neurodegenerative Kennedy´s disease. AR is therefore a crucial therapeutical target. We propose a structure-based drug design strategy that combines our structural information obtained by X-ray crystallography, combinatorial chemistry, and bioinformatics to identify alternative ways to treat prostate cancer by targeting alternative sites on the AR surface.
The laboratory is also interested in the characterization of several orphan receptors with therapeutical potential as drug targets. We aim to visualize several NRs and their key protein and ligand interactions to understand their function in the cell under physiological or pathological conditions. We tackle the biological processes we study from a multidisciplinary approach using several biochemical and biophysical techniques.

Projects

Nuclear Receptors Structure and Function
Crucial to our work is the usage of protein crystallography/X-ray diffraction and other biophysical approaches to visualize the atomic details of NR structure and their key ligand and protein interactions

-Androgen Receptor Structure-Function and Drug Discovery
- Study the role of androgen receptor´s regulatory surfaces AF-2 (Coactivator Binding) and BF-3 (Binding Function 3) pockets in its transcriptional activity.
- Allosteric modulators of AR function as therapeutic drugs to treat prostate cancer using the molecular insights gained from X-ray crystallography and SPR.
- Computational studies on androgen receptor regulatory surfaces. Unravel the relationship between AR regulatory surfaces, their conformational dynamics and biological functions.
- Identification and validation of biological protein partners of the BF-3 pocket.
- Elucidation of the molecular determinants underlying the neuromuscular neurodegenerative disorder (Kennedy´s disease) using a multidisciplinary approach.

Uncharacterized Orphan-receptors Structure-Function and Drug Discovery
-Unravel the crystal structure of uncharacterized orphan receptors and determine their key protein interactions.
-Drug-discovery approach to exploit their clinical applications.

People

		Eva Estébanez-Perpiñá, Ph.D. Group Leader Eva studied at the Universitat Autònoma de Barcelona (UAB), where she obtained her degrees in Biochemistry and Psychology (Psychobiology). She did her Ph.D Thesis under the supervision of the Nobel Laureate Prof. Robert Huber and Prof. Wolfram Bode at the Max-Planck-Institut fuer Biochemie in Martinsried (Germany), where she graduated in 2002. After a short postdoctoral period there she joined in 2003 the lab of Prof. Robert J. Fletterick at the University California, San Francisco (UCSF) to study the structure-function relationships of nuclear receptors such as the androgen receptor and the thyroid receptor. She is at the Institute of Biomedicine, University of Barcelona (IBUB) since January 2008.
		Víctor Buzón Redorta, Ph.D. Postdoctoral Fellow Víctor studied at the UAB, where he obtained his degree in Biochemistry. He did his Ph.D thesis under the supervision of Prof. Cladera at the UAB and later on worked in the lab of Prof. W. Weissenhorn in Grenoble (France). He is specialized in X-ray Crystallography, SPR, ITC, DSC, FTIR and other biophysical/biochemical techniques. He is at the IBUB since February 2010.
		Laia Rodríguez Carbó. Ph.D Student - FPI (Micinn) Laia studied at the UAB, where she obtained her degrees in Biochemistry and Biotechnology. Before starting her Ph.D, Laia worked as research associate in an international pharmaceutical company, where she specialized in cell culture tecniques, cloning, protein expression/purification. Laia is recipient of a FPI-grant from the MICINN. She is at the IBUB since October 2009.
		Sara Busquets Estruch, Ph.D Student Sara studied at the Universitat de Barcelona (UB), where she obtained her degree in Biology. Before starting her Ph.D thesis in our group, Sara has been recipient of the PPL Grant from the Asociación Española Contra el Cáncer and the Passa L´Estiu al Parc Grant from the Scientific Park of Barcelona (PCB) to gain expertise in the lab. She is at the IBUB since June 2010.
		Karolina Zielinska, Research Technician Karolina studied at the Jagiellonian University, Krakow (Poland), where she obtained her degree in Biochemistry. She has been at the University of Cambridge (UK) as senior research technician in the group of Prof. I. Hughes until recently. She specialized in AR and androgen insensitivity syndromes, cell culture, and protein expression/purification. She is at the IBUB since September 2011.
		Erasmus Students 2011-2012 -Lenka Schorova, Erasmus Student, Olomouc University, Czech Republic -Petra Klevcova, Erasmus Student, Olomouc University,Czech Republic
		Previous Lab Members Julie Briot, Erasmus Student, France Imke Baade, Erasmus Student, Germany Lukas Najdekr, Erasmus Student, Czech Republic Alicia Chau, Rotational Student, Washington University, USA Filippo Valente, Erasmus Student, Italy Sergi Ferrero Torrero, Lab Technician

Lab Pictures

Funding

European Union (EU)-Marie Curie Actions International Reintegration Grant (IRG) (Code 224812:AR BF3 Binders)

MICINN (Code:SAF2008-03562: Identificación de las Proteïnas de Unión a BF3)

MICINN (Code:SAF2011-29681: Caracterización Estructural de complejos entre AR y Coreguladores)

MICINN Programa Ramón y Cajal

Fundació La Marató TV3 (Code: Identificación de los Agregados de AR que causan la Atrofia Muscular Espinal Bulbar)

Bayer Schering Pharma (BSP) Berlin (Code FBG7443: Fundació Bosch i Gimpera-UB)

Bayer Schering Pharma (BSP) Berlin (Code FBG28344: Fundació Bosch i Gimpera-UB)

Sponsorship by Medivation Inc. IBUB-Nuclear Receptors:Meet the Family Symposium, Barcelona 21st September, 2011

Publications

2011
Buzón V, Carbó LR, Estruch, SB, Fletterick RJ. and Estébanez-Perpiñá E. A surface on the androgen receptor that allosterically regulates coactivator binding. Invited review, Special issue on Nuclear Receptor Dynamics.
Molecular and Cellular Endocrinology (MCE), in press.

2009
Estébanez-Perpiñá E, and Fletterick RJ. The Androgen Receptor Coactivator Binding Interface. Invited book chapter by Springer-Verlag.
ISBN 9780387691794.

2008
Cruz, L.A, Estébanez-Perpiñá E, Pfaff S., Borngraeber, S., Bao, N., Blethrow, J., Fletterick RJ, and England. P. 6-Azido-7-nitro-1,4,-dihydroquinoxaline-2,3-dione (ANQX) forms and irreversible bond to the active site of the GluR2 AMPA receptor.
J Med Chem. 2008 Sep 25;51(18):5856-60.

Sala, F., Estébanez-Perpiñá E, Balada, F, Garau A., Martí-Carbonell, MA.
Behav Brain Res, 2008 Apr 9; 188(2):348-54

2007
Estébanez-Perpiñá E, Arnold LA, Jouravel N, Togashi M, Blethrow J, Mar E, Nguyen P, Phillips KJ, Baxter JD, Webb P, Guy RK, Fletterick RJ. A surface on the androgen receptor that allosterically regulates coactivator binding.
Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16074-9.

Estébanez-Perpiñá E, Jouravel N, and Fletterick RJ. Perspectives on designs of antiandrogens for prostate cancer.
Expert Opinion on Drug Discovery. 2007 Oct, Vol. 2, No. 10, Pages 1341-1355

Estébanez-Perpiñá E, Arnold LA, Jouravel N, Togashi M, Blethrow J, Mar E, Nguyen P, Phillips KJ, Baxter JD, Webb P, Guy RK, Fletterick RJ. Structural insight into the mode of action of a direct inhibitor of coregulator binding to the thyroid hormone receptor.
Mol Endocrinol. 2007 Dec;21(12):2919-28.

Arnold LA, Kosinski A, Estébanez-Perpiñá E, Fletterick RJ, Guy RK. Inhibitors of the interaction of a thyroid hormone receptor and coactivators: preliminary structure-activity relationships.
J Med Chem. 2007 Nov 1;50(22):5269-80.

2006
Arnold LA, Estébanez-Perpiñá E, Togashi M, Shelat A, Ocasio CA, McReynolds AC, Nguyen P, Baxter JD, Fletterick RJ, Webb P, Guy RK. A high-throughput screening method to identify small molecule inhibitors of thyroid hormone receptor coactivator binding.
Sci STKE. 2006 Jun 27;2006(341):pl3.

2005
Arnold LA, Estébanez-Perpiñá E, Togashi M, Jouravel N, Shelat A, McReynolds AC, Mar E, Nguyen P, Baxter JD, Fletterick RJ, Webb P, Guy RK. Discovery of small molecule inhibitors of the interaction of the thyroid hormone receptor with transcriptional coregulators.
J Biol Chem. 2005 Dec 30;280(52):43048-55.

Estébanez-Perpiñá E, Moore JM, Mar E, Delgado-Rodrigues E, Nguyen P, Baxter JD, Buehrer BM, Webb P, Fletterick RJ, Guy RK. The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor.
J Biol Chem. 2005 Mar 4;280(9):8060-8.

Contact

If you are interested in joining the lab as postdoc, PhD student or research assistant please send us your CV and cover letter:
evaestebanez@ub.edu

Institut de Biomedicina (IBUB), Universitat de Barcelona (UB)
Parc Cientific de Barcelona (PCB)
Ph office: (00-34) 93-403-11-19
Cell Ph: (00-34) 696-73-4226
Edifici Helix (Lab ES03A08, Office B08)
Baldiri Reixac, 15-21, 08028 Barcelona

News

September, 2011
Francesc Villarroya and Eva Estébanez organize the IBUB-Symposia: Nuclear Receptors: Meet the Family
September 21st, Aula Magna, Faculty of Biology, UB, Avda Diagonal 645, Barcelona
Program and Invited Speakers

June, 2011
Four groups of the IBUB (M. Cascante, M. Pastor, C. Ciudad and E. Estébanez) in the Oncocat network.
The Oncocat network has been created to promote synergies in research in cancer in Catalonia.
http://www.biocat.cat/es/conoce-biocat

October, 2010
Eva Estébanez together with Xavier Salvatella (IRB, Barcelona) and Leila Luheshi (Cambridge Univ) have been awarded a collaborative project by the Marató de TV3 with 397,000 Euro to study Kennedy´s disease, a rare neurodegenerative disease
http://www.tv3.cat/marato/es/projectes_financats_2009.htm

May, 2009
The Nobel Laureate in Chemistry Robert Huber gives a conference titled Proteases and Their Regulation, from Molecular Structures to Application invited by Francesc Villarroya and Eva Estébanez.
Aula Magna, Faculty of Biology. Many ex-alumni of Robert Huber were also present in the audience