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Vascular Biology & Cancer Microenvironment

We study the role of blood vessels, and of endothelial cells, in regulating normal organ function and in disease. In detail, we study cancer (solid and hematologic) as a systemic disease that involves (and requires) blood vessels for its onset and progression.

In addition to the role of blood vessels, we also study the involvement of bone marrow-derived cells and of metabolic systemic signals in cancer onset and progression.

Research Team

Ana Magalhães
Senior Postdoctoral Researcher
anamagalhaes@medicina.ulisboa.pt

Diogo Coutinho
Lab Technician
dcoutinho@medicina.ulisboa.pt

Emanuel Estevez de Oliveira
MSc Student
emanueloliveira@medicina.ulisboa.pt

Miguel Esperança Martins
PhD Student
miguel.martins@medicina.ulisboa.pt

Pedro Marreiros
MSc Student
pmarreiros@medicina.ulisboa.pt

Sofia Esteves
Trainee
sofia.esteves@medicina.ulisboa.pt

Teresa L Serafim
Senior Postdoctoral Researcher
tserafim@medicina.ulisboa.pt

Research Areas

  • Tumor Angiogenesis
  • Tumor Metabolism
  • Bone-Marrow

Ongoing Research Projects

2020/2021 Regulation of Breast Cancer Intravasation. Coordinator: Ana Magalhães. Funding Agency: Fundo iMM-Laço.

2018/2021 Como o colesterol promove a metastização em cancro de mama. Coordinator: Sérgio Dias. Funding Agency: Fundação para a Ciência e Tecnologia.

Awards

2013 Laço Award for Breast Cancer Research

2004 Pfizer Biomedical Research Prize, "Sociedade de Ciências Médicas/Pfizer".

2004 "Pulido Valente/FCT Prize" for the Best paper in Oncology Research in Portugal.

Selected Publications

Rodrigues NV, Correia DV, Mensurado S, Nóbrega-Pereira S, deBarros A, Kyle-Cezar F, Tutt A, Hayday AC, Norell H, Silva-Santos B, Dias S (2018). Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of Human Vγ9Vδ2 T Cells. Cancer Immunology Research 6(4):448-457.

Nóbrega-Pereira S, Caiado F, Carvalho T, Matias I, Graça G, Gonçalves LG, Silva-Santos B, Norell H, Dias S (2018). VEGFR-2-mediated reprogramming of mitochondrial metabolism regulates the sensitivity of acute myeloid leukemia to chemotherapy. Cancer Research 78(3):731-741.

dos Santos CR, Domingues G, Matias I, Matos J, Fonseca I, de Almeida JM, Dias S (2014). LDL-cholesterol signaling induces breast cancer proliferation and invasion. Lipids in Health and Disease 13:16.

Caiado F, Carvalho T, Rosa I, Remédio L, Costa A, Matos J, Heissig B, Yagita H, Hattori K, da Silva JP, Fidalgo P, Dias Pereira A, Dias S (2013). Bone marrow-derived CD11b+Jagged2+ cells promote epitelial to mesenchymal transition and metastization in colorectal cancer. Cancer Research 73(14):4233-46.

Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs. Fibrogenesis Tissue Repair. (invited review) 12;5(1):4. (2012)

Casalou C, Costa A, Carvalho T, Gomes AL, Zhu Z, Wu Y, Dias S. Cholesterol Regulates VEGFR-1 (FLT-1) Expression and Signaling in Acute Leukemia Cells. Mol Cancer Res. 9(2):215-24. (2011)

Real C, Remedio L, Caiado F, Igreja C, Borges C, Trindade A, Pinto-do-Ó P, Hyagita H, Duarte A, Dias S. Bone marrow-derived Endothelial Progenitors expressing Delta-like 4 (Dll4) regulate tumor angiogenesis. PloS One. 6(4):e18323. (2011)

Schmidt T, Kharabi Masouleh B, Loges S, Cauwenberghs S, Fraisl P, Maes C, Jonckx B, De Keersmaecker K, Kleppe M, Tjwa M, Schenk T, Vinckier S, Fragoso R, De Mol M, Beel K, Dias S, et al. Loss or Inhibition of Stromal-Derived PlGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1(+) Leukemia. Cancer Cell. 14;19(6):740-53. (2011)

Caiado F, Carvalho T, Silva F, Castro C, Clode N, Dye JF and Dias S. Fibrin E modulates endothelial progenitors adhesion, differentiation and angiogenic growth factor production and promotes wound healing. Biomaterials, 32(29):7096-105 (2011)

Gomes AL, Carvalho T, Torre C, Serpa J and Dias S. Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF1:CXCR4 axis. Blood 115(19):3886-94 (2010)

Epiphanio S, Campos MG, Pamplona A, Carapau D, Pena AC, Ataíde R, Monteiro CA, Félix N, Costa-Silva A, Marinho CR, Dias S, Mota MM. VEGF promotes malaria-associated acute lung injury in mice. PLoS Pathogens. 6(5):e1000916. (2010)

Serpa J, Caiado F, Carvalho T, Torre C, Goncalves LG, Casalou C, Lamosa P, Rodrigues M, Zhu Z, Lam EW, Dias S.Butyrate rich colonic microenvironment is a relevant selection factor for metabolically adapted tumour cells. J Biological Chemistry. 285(50):39211-23. (2010)

Caiado F, Real C, Carvalho T, Dias S. Notch pathway modulation on bone marrow-derived vascular precursor cells regulates their angiogenic and wound healing potential. PLoS One. 3(11):e3752. Epub 2008 Nov 18 (2008)

Kerbel RS, Benezra R, Lyden DC, Hattori K, Heissig B, Nolan DJ, Mittal V, Shaked Y, Dias S, Bertolini F, Rafii S.Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas. Proc Natl Acad Sci U S A. 105(34):E54; author reply E55. (2008)

Casalou C, Fragoso R, Nunes JF and Dias S. VEGF/PLGF induces leukemia cell migration via P38/ERK1/2 kinase pathway, resulting in Rho GTPases activation and caveolae formation. Leukemia. 21: 1590-1594 (2007).

Santos SCR et al and Dias S. VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing. Experimental Cell Research. 313(8):1561-74 (2007)

Fragoso R, Pereira T, Wu Y, Zhu Z, Cabeçadas J and Dias S. VEGFR-1 (FLT-1) activation modulates acute lymphoblastic leukemia localization and survival within the bone marrow, determining the onset of extramedullary disease. Blood, 107(4):1608-16 (2006).

Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, Jin DK, Dias S, et al.. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Medicine. 10(1):64-71 (2004).

Constantino Rosa Santos S and Dias S. Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia. Blood. 103(10): 3883-9 (2004).

group leader :
Sérgio Dias