Functional cancer genomics. IP: Antoni Hurtado Rodriguez

Presentation

The Group investigates the mechanisms of hormone resistance and breast cancer.

Breast cancer is the most common cancer in women of developed countries, and at least two thirds of breast tumors are positive for the expression of Estrogen Receptor alpha (ER). ER is a transcription factor that binds to estrogen and activates transcription in mammary cells. ER drives proliferation of this breast cancer type and current treatments pursuit targeting its activity.

Unfortunately, a large number of patients do not respond to these therapies from the beginning or stop responding during treatment. In our group, we intend to determine how these ER inhibitory drugs work and we also investigate the molecular mechanisms of resistance.

Antoni Hurtado Rodriguez
Ramón y Cajal fellow
toni.hurtado@ub.edu

Jose Angel Palomeque
Master's student
jpalomal7@alumnes.ub.edu

Shixiong Wang
Post-doc/guest researcher
shixiong.wang@ncmm.uio.no

Sherisa Wirabuana
Erasmus student
From the HAN Univ. of Applied Sciences in Nijmegen, The Netherlands
agathasherissa@gmail.com

Albert Gil Arrieta
Interim student of medicine UB (Clínic)
albertgilarrieta@gmail.com

Tamara Parracho Matínez
Final work of the Degree in Biomedicine
From the UB, Clinic.
tparrama21@alumnes.ub.edu

Tamoxifen and Aromatase Inhibitors (AI) are the most used anti-estrogen drugs for adjuvant therapy in breast cancer patients, but patients frequently fail to respond to those treatments. To the present date, several works have described distinct factors that influence the function of ER and ultimately dictate the efficacy of the anti-estrogen therapies. The presence of these cooperative factors raises a new level of complexity for ER transcriptional regulation and endocrine response. Our group investigates the mechanisms of hormone-resistance. In particular, our research project is structured in two comprehensive and often overlapping areas.

How anti-ER drugs performs: One area entails chemical systems approaches to: (1) functionally understand how anti-ER drugs perform their repressive effects and (2) identify novel mechanism by which hormone-resistant cells overcome ER inhibition.

Specifically, we are employing a combination of targeted proteomics, drug screenings, highthroughput sequencing of chromatin and sequencing of de novo transcripts (by means of GRO-seq) in the projects related with this part of my research.

How drugs influence tumor growth: The second area involves in vivo approaches from patient derived xenographs of breast cancer tumors. With this research, we aim to test how drugs identified in our drug screening influence the tumor growth of breast cancer tumors. Moreover, we will validate which compounds might be used as alternative therapies for patients with poor response to current anti-ER therapies using hormone-resistant breast cancer in vivo models.

  • RESCUER-Resistance Under Combinatorial Treatment in ER+ and ER- Breast Cancer

PI: Antoni Hurtado Rodriguez (líder paquet treball 11 (WP11)
Funding entity: European Commission, Horizon 2020
Reference: …………..
Period: 2020-2025
Amount: 465.000 euros

  • Elucidación en cánceres de mama y endometrio de los mecanismos de acción del compuesto hydroxy-tamoxifeno

PI: Antoni Hurtado Rodriguez
Funding entity: MINECO, proyectos I+D Excelencia
Reference: PGC2018-099175-B-I00
Period: 2019-2021
Amount: 180.000 euros

For more information for PI publications click in the links:
ORCID: https://orcid.org/0000-0002-0145-4763
Google schoolar: https://scholar.google.com/citations?hl=en&user=cKn-7nQAAAAJ&view_op=list_works&sortby=pubdate

S Wang, S Singh, M Katika, S Lopez-Aviles, A Hurtado. High throughput chemical screening reveals multiple regulatory proteins on FOXA1 in breast cancer cell lines. Int J Mol Sci. 2018 Dec 19; 19 (12). pii: E4123. doi: 10.3390/ ijms 19124123. PMID 30572598

S Vdovikova, S Gilfillan, S Wang, M Dongre, SN Wai, A Hurtado. Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles. Scientific reports 8 (1), 7434

Mari Kyllesø Halle, Ingvild Løberg Tangen, Hege Fredriksen Berg, Erling Andre Hoivik, Karen K Mauland, Kanthida Kusonmano, Anna Berg, Antoni Hurtado, Karl Henning Kalland, Anne M Øyan, Ingunn Stefansson, Olav K Vintermyr, Henrica M Werner, Ingfrid S Haldorsen, Jone Trovik, Helga B Salvesen, Camilla Krakstad. HER2 expression patterns in paired primary and metastatic endometrial cancer lesions. Br J Cancer. 2018 Feb 6; 118 (3): 378-387. doi: 10.1038/ bjc. 2017.422. Epub 2017 Nov 23. PMID: 29169184

Thomas Fleischer, Xavier Tekpli, Anthony Mathelier, Shixiong Wang, Daniel Nebdal, Hari P Dhakal, Kristine Kleivi Sahlberg, Ellen Schlichting, Anne-Lise Børresen-Dale, Elin Borgen, Bjørn Naume, Ragnhild Eskeland, Arnoldo Frigessi, Jörg Tost, Antoni Hurtado, Vessela N Kristensen. DNA methylation at enhancers identifies distinct breast cancer lineages. Nat Commun. 2017 Nov 9; 8(1): 1379. doi: 10.1038/ s41467-017-00510-x. PMID: 29123100

Elisa Fiorito, Yogita Sharma, Siv Gilfillan, Shixiong Wang, Sachin Kumar Singh, Somisetty V Satheesh, Madhumohan R Katika, Alfonso Urbanucci, Bernd Thiede, Ian G Mills, Antoni Hurtado. CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions. Nucleic Acids Res. 2016 Dec 15; 44 (22): 10588-10602. Epub 2016 Sep 15. PMID: 27638884

Ingvild Løberg Tangen, Camilla Krakstad, Mari K Halle, Henrica MJ Werner, Anne M Øyan, Kanthida Kusonmano, Kjell Petersen, Karl Henning Kalland, Lars A Akslen, Jone Trovik, Antoni Hurtado, Helga B Salvesen. Switch in FOXA1 status associates with endometrial cancer progression. PLoS One. 2014 May 21; 9(5): e98069. doi: 10.1371/ journal.pone. 0098069. eCollection 2014. PMID: 24849812

David A Quigley, Elisa Fiorito, Silje Nord, Peter Van Loo, Grethe Grenaker Alnæs, Thomas Fleischer, Jorg Tost, Hans Kristian Moen Vollan, Trine Tramm, Jens Overgaard, Ida R Bukholm, Antoni Hurtado, Allan Balmain, Anne-Lise Børresen-Dale, Vessela Kristensen. The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen‐receptor positive tumors. Mol Oncol. 2014 Mar; 8(2): 273-84. doi: 10.1016/ j.molonc. 2013.11.008. Epub 2013 Dec 3. PMID: 24388359

E Fiorito, MR Katika, A Hurtado. Cooperating transcription factors mediate the function of estrogen receptor. Chromosoma. 2013 Mar; 122 (1-2): 1-12. doi: 10.1007/ s00412-012- 0392-7. Epub 2012 Nov 29. PMID: 23192763

MR Katika, A Hurtado. A functional link between FOXA1 and breast cancer SNPs. Breast Cancer Res. 2013 Feb 18; 15 (1): 303. doi: 10.1186/ bcr3360. PMID: 23427833

S Gilfillan, E Fiorito, A Hurtado. Functional genomic methods to study estrogen receptor activity. J Mammary Gland Biol Neoplasia. 2012 Jun; 17(2): 147-53. doi: 10.1007/ s10911-012- 9254-4. Epub 2012 May 16. PMID: 22588661

Kelly A Holmes, Antoni Hurtado, Gordon D Brown, Rosalind Launchbury, Caryn S Ross-Innes, James Hadfield, Duncan T Odom, Jason S Carroll. Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells. Proc Natl Acad Sci U S A. 2012 Feb 21; 109 (8): 2748-53. doi: 10.1073/ pnas. 1018863108. Epub 2011 May 2. PMID: 21536917

Daniel G Holland, Angela Burleigh, Anna Git, Mae A Goldgraben, Pedro A Perez‐Mancera, Suet‐Feung Chin, Antonio Hurtado, Alejandra Bruna, H Raza Ali, Wendy Greenwood, Mark J Dunning, Shamith Samarajiwa, Suraj Menon, Oscar M Rueda, Andy G Lynch, Steven McKinney, Ian O Ellis, Connie J Eaves, Jason S Carroll, Christina Curtis, Samuel Aparicio, Carlos Caldas. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med. 2011 Mar; 3 (3): 167-80. doi: 10.1002/ emmm. 201100122. Epub 2011 Feb 18. PMID: 21337521

A Hurtado, KA Holmes, CS Ross-Innes, D Schmidt, JS Carroll. FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat Genet. 2011 Jan; 43 (1): 27-33. doi: 10.1038/ ng. 730. Epub 2010 Dec 12. PMID: 21151129

  • Offers from the University of Barcelona::

Work UB

  • Offers from the Research Group:

- Post-doctoral bioinformatic position in functional cancer genomics and proteomics
- PhD student: we offer a 3 years contract and the candidate might have masters in biomedicine.
- TFG, master and Erasmus students are also welcome.