Cancer Biology Unit
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
» Ongoing Research Projects
2011/14 - Identification of new CK2 regulatos with impact on PTEN function in leukemia, FCT (PTDC/SAU-ONC/113202)
2010/13 - Cell-intrinsic and microenvironmental signals intertwined: novel targets for therapeutic intervention in acute lymphoblastic leukemia?, FCT (Project PTDC/SAU-OBD/104816).
2010/12 - Reciprocal regulation between TAL1 and miRNA expression in T-cell leukemia, NRS/LPCC and Terry Fox Foundation.
2009/12 - Regulation of ZAP-70 and PTEN activity and stability in chronic lymphocytic leukemia: prognostic and therapeutic implications, FCT (PIC/IC/83193).
2009/12 - Clinical implications of activation of PI3K/Akt signaling pathway in primary adult acute lymphoblastic leukemia. Collaboration with UIC, IMM Flow cytometry Unit, HSM and Hospital dos Capuchos, FCT (PIC/IC/83023).
» Science and Society Activities
Dr. José Andrés Yunes (Centro Infantil Boldrini, São Paulo, Brazil)
Dr. Benedict Seddon (NIMR, London, UK)
Dr. Scott Durum (CCR, Frederick, Maryland, USA)
Prof. Paul Coffer (UMC, Utrecht, The Netherlands)
Dr. Jocelyne Demengeot (IGC, Oeiras, Portugal)
Prof. João Gonçalves (Faculdade de Farmácia, Lisboa, Portugal)
Dr. Jules Meijerink (EMC, Rotterdam, The Netherlands.)
Dr. Alberto Martelli (Cellular Signalling Laboratory, University of Bologna, Italy)
Prof. Gerry Graham (Glasgow University, Glasgow, UK)
Dr. Nicholas Leslie (University of Dundee, Dundee, UK)
» Selected Publications
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
P.P. Zenatti, D. Ribeiro, W. Li, L. Zuurbier, M.C. Silva, M. Paganin, J. Tritapoe, J.A. Hixon, A.B. Silveira, B.A. Cardoso, L.M. Sarmento, N. Correia, M. L. Toribio, J. Kobarg, M. Horstmann, R. Pieters, S.R. Brandalise, A.A. Ferrando, J.P. Meijerink, S.K. Durum, J.A. Yunes, J.T. Barata (2011). Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia. Nature Genetics 43 (10): 932-939.
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