João Barata Lab
The Cancer Biology Unit aims to establish a dynamic research vector on cancer biology, with particular emphasis on hematological malignancies. There is mounting evidence that tumor cells interact with the surrounding environment in a bi-directional manner resulting in the acquisition of a competitive advantage by the malignant cells. Therefore, cancer progression is not exclusively dependent on tumor cell-autonomous alterations. Our research focuses on the role that both cell-intrinsic aberrations and microenvironmental factors might play during tumorigenesis. Our main model has been acute T-cell leukemia. In parallel, we are interested in understanding the regulation of normal human T-cell development by external signals. Our goal is to characterize the cellular and molecular mechanisms implicated in the acquisition of a selective advantage by malignant/leukemic cells over their normal counterparts, focusing on the dissection of signaling pathways activated by cell-intrinsic events and extra-cellular factors. Ultimately, this will allow the identification of molecular targets for therapeutic intervention and the pre-clinical evaluation of therapeutic agents against such targets.
» Research Areas
» Group Leader
» Research Team
João Taborda Barata
PhD (2003) in Biomedical Sciences at Harvard Medical School (USA) and University of Porto
Postdoctoral research at IMM, Pasteur Institute (France) and Utrecht University (The Netherlands)
Awarded the Pfizer Award for Basic Research in 2008 and for Clinical Research in 2011
FCT Investigator (Consolidator)
Invited Associate Professor at the Faculty of Medicine, University of Lisbon
» Ongoing Research Projects
2013/15 - Do miRNAs and TAL1 crosstalk? New insights into the regulation and function of a major T-cell oncogene, FCT (PTDC/BIM-ONC/1548).
2012/15 - Dissecting the impact of IL7R gain-of-function mutations in T-cell leukemia, FCT (Project PTDC/SAU-ONC/122428/2010).
2011/14 - Identification of new CK2 regulators with impact on PTEN function in leukemia, FCT (PTDC/SAU-ONC/113202).
» Science and Society Activities
José Andrés Yunes (Centro Infantil Boldrini, São Paulo, Brazil)
Benedict Seddon (NIMR, London, UK)
Scott Durum (CCR, Frederick, Maryland, USA)
Paul Coffer (UMC, Utrecht, The Netherlands)
Jules Meijerink (EMC, Rotterdam, The Netherlands)
Alberto Martelli (Cellular Signalling Laboratory, University of Bologna, Italy)
Main internal collaborations:
Ana E. Sousa, Bernardo Gonçalves, Bruno Silva-Santos, João Gonçalves, Luís F. Moita, Sérgio Dias, Sérgio Almeida
Participation in Maratona da Saúde 2013-2014 (TV interviews and the match “Scientists vs Benfica veterans”).
The lab frequently engages in guided visits to IMM from university and high school student groups.
» Selected Publications
2013 Silver Medal for Distinct Services from the Portuguese Ministry of Health. (awarded to J.T. Barata)
2012 Best Immunology Paper Award. Portuguese Society of Imunology (SPI).
2011 Pfizer Award in Clinical Research - Sociedade de Ciências Médicas de Lisboa
2010 NRS/LPCC and “TERRY FOX" Grant/Prize for Research in Oncology (awarded to J.T. Barata)
2009 Pulido Valente Science Prize in Translational Molecular Oncology (awarded to A. Silva)
2008 Pfizer Award in Basic Research - Sociedade de Ciências Médicas de Lisboa
2005 Grant Award “Programa de Apoio à Investigação em Onco-Hematologia” - Associação Portuguesa Contra a Leucemia (APCL)/Portuguese Association Against Leukemia (awarded to J.T. Barata)
2004 Prize “Programa Gulbenkian de Estímulo à Investigação 2004” - Fundação Calouste Gulbenkian (awarded to A. Silva)
2002 LabMED Award – 3rd Place - “An IL-7-dependent Human Leukemia T-Cell Line as a Valuable Tool for Drug Discovery in T-ALL” (awarded to J.T. Barata et al.)
» Useful Links
- R.D. Mendes*, L.M. Sarmento*, K. Canté-Barrett, L. Zuurbier, J. Buijs-Gladdines, V. Povoa, W.K. Smits, M. Abecassis, J.A. Yunes, E. Sonneveld, M.A. Horstmann, R. Pieters, J.T. Barata**, and J.P.P. Meijerink** (2014). PTEN micro-deletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events. Blood 2014 Jun 5. pii: blood-2014-03-562751. [Epub ahead of print] *co-first authors; ** co-senior authors
- A.M. Gomes, M.V.D. Soares, P. Ribeiro, J. Caldas, V. Póvoa, L.R. Martins, A. Melão, A. Serra-Caetano, A.B. de Sousa, J. F. Lacerda, J.T. Barata (2014). Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels. Haematologica 99 (6): 1062-1068.
- A. Lonetti*, I.L. Antunes*, F. Chiarini, E. Orsini, F. Buontempo, F. Ricci, P.L. Tazzari, P. Pagliaro, F. Melchionda, A. Pession, A. Bertaina, F. Locatelli, J.A. McCubrey, J.T.Barata**, A.M. Martelli** (2014). Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T-cell acute lymphoblastic leukemia. Leukemia 28 (6): 1196–1206. *co-first authors; ** co-senior authors
- L.R. Martins, P. Lúcio, A. Melão, I. Antunes, B.A. Cardoso, R. Stansfield, M.T. Bertilaccio, P. Ghia, D. Drygin, M.G. Silva, J.T. Barata (2014). Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia. Leukemia 28 (1): 179–182.
- J.T. Barata (2013). IL-7Rα: Mr Hyde's twists and turns. Blood 122 (26): 4151-4152.
- N. Correia, K. Durinck, A.P. Leite, M. Ongenaert, P. Rondou, F. Speleman, F.J. Enguita, J.T. Barata (2013). Novel TAL1 targets beyond protein-coding genes: identification of TAL1-regulated microRNAs in T-cell acute lymphoblastic leukemia. Leukemia 27 (7): 1603-1606.
- B.A. Cardoso, S.F. de Almeida, A.B. Laranjeira, M. Carmo-Fonseca, J.A. Yunes, P.J. Coffer, J.T. Barata (2011). TAL1/SCL is downregulated upon histone deacetylase inhibition in T-cell acute lymphoblastic leukemia cells. Leukemia 25 (10): 1578-1586.
- A. Silva, A.B. Laranjeira, L.R. Martins, B.A. Cardoso, J. Demengeot, J.A. Yunes, B. Seddon, J.T. Barata (2011). IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Research 71 (14): 4780-4789.
- A. Silva, A. Gírio, I. Cebola, C.I. Santos, F. Antunes, J.T. Barata (2011). Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells. Leukemia 25 (6): 960-967.
- L.R. Martins, P. Lúcio, M.C. Silva, P. Gameiro, M.G. Silva, J.T. Barata (2010). Targeting CK2 Overexpression and Hyperactivation as a Novel Therapeutic Tool in Chronic Lymphocytic Leukemia. Blood 116 (15):2724-2731
- C.M. Henriques, J. Rino, R.J. Nibbs, G.G. Graham, J.T. Barata (2010). IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Rα in T cells. Blood 115 (16): 3269-3277.
- P.Y. Jotta, M.A. Ganazza, A. Silva, M.B. Viana, M.J. da Silva, L.J.G. Zambaldi, J.T. Barata, S.R. Brandalise, J.A. Yunes (2010). Negative prognostic impact of PTEN mutation in pediatric T-cell acute lymphoblastic leukemia. Leukemia 24 (1): 239-242.
- B.A. Cardoso, L.R. Martins, C.I. Santos, L.M. Nadler, V.A. Boussiotis, A.A. Cardoso, J.T. Barata (2009).Interleukin-4 stimulates proliferation and growth of T-cell acute lymphoblastic leukemia cells by activating mTOR signaling. Leukemia 23 (1):206-208.
- A. Silva, J.A. Yunes, B.A. Cardoso, L.R. Martins, P.Y. Jotta, M. Abecasis, A.E. Nowill, N.R. Leslie, A.A. Cardoso, J.T. Barata (2008) PTEN Posttranslational Inactivation and Hyperactivation of the PI3K/Akt Pathway Sustain Primary T Cell Leukemia Viability. Journal of Clinical Investigation 118 (11): 3762-3774.
- J.T. Barata, A. Silva, J.G. Brandão, L.M. Nadler, A.A. Cardoso, V.A. Boussiotis (2004) Activation of PI3K is Indispensable for Interleukin 7-Mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells. Journal of Experimental Medicine 200 (5): 659-669.
- J.T. Barata, V.A. Boussiotis, J.A. Yunes, A.A. Ferrando, L.A. Moreau, J.P. Veiga, S.E. Sallan, A.T. Look, L.M. Nadler, A.A. Cardoso (2004). IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL. Blood 103 (5): 1891-1900.
- J.T. Barata, A.A. Cardoso, L.M. Nadler, V.A. Boussiotis (2001). Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27kip1. Blood 98 (5): 1524-1531.
Cancer Biology Unit - Non-official website