Breast cancer risk and progression Lab


​Miquel Angel Pujana - Group Leader
Francesca Mateo - Associate researcher
Carmen Herranz - PhD Student
Anabel Extremera - Lab technician

To learn more about who we are and what we do please visit us at
http://www.cancersystemsbiology.cat/
  • Description
  • Publications
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The main themes of our research are based on better understand breast cancer development, the emergence of subtypes, and their therapeutic response/resistance. Particularly, our studies are focused on triple-negative (TNBC) and BRCA1-mutated (germline) breast cancer, and resistance to endocrine and mTOR-targeted therapies.
 
  • The study of TNBC (and related neoplastic conditions) aims to predict and evaluate therapeutic approaches for this “orphan targeted” subtype. To accomplish this objective, we integrate omic data and model context-specific signaling pathways.
  • The study of BRCA1-mutated breast cancer is led by key observations that described common genetic variation in HMMR associated with breast cancer risk, and interplay of HMMR-BRCA1 regulating mammary epithelial cell differentiation (Pujana et al., Nature Genetics 2007; Maxwell et al., PLoS Biology 2011; Blanco et al., PLoS One 2015). In this scenario, we aim to test modification of penetrance in vivo, using novel mice models. In parallel, through genome sequencing of resilient cases we aim to identify mutations/variants with large protective effects.
  • The study of endocrine resistance aims to identify targeted approaches that may overcome or reduce this problem. For this, cellular and PDX models are generated and comprehensively analyzed.
  • The study of resistance to mTOR inhibition is linked to a better understanding of the mechanism of metastasis and how they may be impaired. This study is also connected to the analysis of rare neoplastic disease appearing almost exclusively in childbearing women and characterized by lung metastatic cells of unknown origin (lymphangioleiomyomatosis, LAM).
  • Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EE, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JW, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR & Pujana MA. “Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition”. Oncogene doi: 10.1038/onc.2016.427, 2016.

  • Serra-Musach J, Mateo F, Capdevila-Busquets E, de Garibay GR, Zhang X, Guha R, Thomas CJ, Grueso J, Villanueva A, Jaeger S, Heyn H, Vizoso M, Pérez H, Cordero A, Gonzalez-Suarez E, Esteller M, Moreno-Bueno G, Tjärnberg A, Lázaro C, Serra V, Arribas J, Benson M, Gustafsson M, Ferrer M, Aloy P & Pujana MA. “Cancer network activity associated with therapeutic response and synergism”. Genome Medicine 24;8(1):88, 2016.

  • Pujana MA. “Integrating germline and somatic data towards a personalized cancer medicine”. Trends in Molecular Medicine 20(8):413-5, 2014.

  • Aguilar H, Urruticoechea A, Halonen P, Kiyotani K, Mushiroda T, Barril X, Serra-Musach J, Islam A, Caizzi L, Di Croce L, Nevedomskaya E, Zwart W, Bostner J, Karlsson E, Pérez Tenorio G, Fornander T, Sgroi DC, Garcia-Mata R, Jansen MP, García N, Bonifaci N, Climent F, Soler MT, Rodríguez-Vida A, Gil M, Brunet J, Martrat G, Gómez-Baldó L, Extremera AI, Figueras A, Balart J, Clarke R, Burnstein KL, Carlson KE, Katzenellenbogen JA, Vizoso M, Esteller M, Villanueva A, Rodríguez-Peña AB, Bustelo XR, Nakamura Y, Zembutsu H, Stål O, Beijersbergen RL & Pujana MA. “VAV3 mediates resistance to breast cancer endocrine therapy”. Breast Cancer Research 16(3):R53, 2014.

  •  Maxwell CA, (CIMBA consortium) & Pujana MA. “Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer”. PLoS Biology 9(11):e1001199, 2011.

  •  Aguilar H, Solé X, Bonifaci N, Serra-Musach J, Islam A, López-Bigas N, Méndez-Pertuz M, Beijersbergen RL, Lázaro C, Urruticoechea A & Pujana MA. “Biological reprogramming in acquired resistance to endocrine treatment of breast cancer”. Oncogene 29(45):6071-83, 2010.

  •   Pujana MA, J-DJ Han, LM Starita, K Stevens, Tewari M, Ahn JS, Rennert G, Moreno V, Kirchhoff T, Gold B, Assmann V, Elshamy WM, Rual JF, Levine D, Rozek LS, Gelman RS, Gunsalus KC, Greenberg RA, Sobhian B, Bertin N, Venkatesan K, Ayivi-Guedehoussou N, Solé X, Hernández P, Lázaro C, Nathanson KL, Weber BL, Cusick ME, Hill DE, Offit K, Livingston DM, Gruber SB, Parvin JD & Vidal M. “Network modeling establishes a link between breast cancer susceptibility and centrosome dysfunction”. Nature Genetics 39(11): 1338-49, 2007.
Title: Therapeutic modeling of triple-negative breast cancer.
Supporting Agency: Instituto Salud Carlos III.
 
Title: Targeting metastatic breast cancer.
Supporting Agency: in collaboration with ICO researchers.
 
Title: Lymphangioleiomyomatosis; tissue of origin, models and therapeutic approaches.
Supporting Agencies: Telemaratón Spanish TVE “Todos Somos Raros, Todos Somos Únicos” and Spanish Association of LAM (AELAM).
 
Title: Identification of breast cancer genes and, in turn, mutations/variants that provide strong protective effects.
Supporting Agency: in collaboration with ICO researchers
Collaborations
IDIBELL campus:
Hereditary Breast Cancer, IDIBELL: Joan Brunet, Conxi Lázaro.
Cancer Epigenetics and Biology, IDIBELL: Manel Esteller and Eva González-Suárez.
 
Lymphangioleiomyomatosis:
AELAM, Spanish Association of LAM Patients.
Clinicians: A Xaubet, A Roman, A Casanovas, J Ancochea, C Valenzuela, M Molina-Molina, R Laporta, M Piedad Ussetti.
International Consortium for LAM Epidemiological Study.
 
Fanconi anemia and BRCAX:
Jordi Surrallés (UAB, Barcelona).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
 
Breast and ovarian cancer risk:
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Spanish Collaborative Research Group in Breast Cancer (SOLTI).
Genetics of Acquired Endocrine Resistance: Hitoshi Zembutsu (University of Tokyo).
Genetics of Breast Cancer Metastasis: John M. Martens (Erasmus University Medical Center).
Molecular Mechanisms of Acquired Endocrine Resistance: Roderick Beijersbergen (Netherlands Cancer Institute).
Biomarkers and HER2: Gema Moreno-Bueno (MD Anderson and UA Madrid).
Therapies and drug screening: NCATS/NIH, Dr. Marc Ferrer.
BRCA1-associated tumorigenesis: Mary-Helen Barcellos-Hoff (UCSF).
BRCA1 and regulators: Chiara Gorrini (Campbell Institute, Toronto).
RNFs and breast tumorigenesis: Razq Hakem (U Toronto).
Breast Cancer Metastasis: Roger Gomis (IRB, Barcelona).

Cancer bioinformatics and networks:
Francesc Comellas (Polytechnic University of Catalonia).
Júlio Sáez-Rodríguez (RWTH-Aachen University).
Patrick Aloy (IRB, Barcelona).
Roger Guimerà (URV, Tarragona).
To inquiere about open positivas please contact:

​Dr. Miguel Angel Pujana
Program Against Cancer Therapeutic Resistance, ProCURE
Catalan Institute of Oncology
Bellvitge Biomedical Research Institute, IDIBELL
3 floor, LRT1, Hospital Duran i Reynals
Gran Via 199-203, 08907 L’Hospitalet de Llobregat
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