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Vascular Morphogenesis

The vascular tree enables appropriate blood distribution and supply to all tissues in several multicellular organisms. The vascular network is essential for embryonic development, growth and wound healing. Importantly, many human disorders arise from mis-patterning of blood vessels, such as in diabetic retinopathy, ischemia, stroke, or tumour angiogenesis.

The formation of a functional vascular network requires simultaneous peripheral sprouting of newly formed blood vessels into avascular tissues and remodelling of the primitive amorphous vascular plexus into a hierarchical network of arteries, capillaries and veins. These two processes are tightly regulated by molecular communication between cells in the tissue and endothelial cells (the cells lining the blood vessels). Notably, it is now becoming evident that endothelial cells need to coordinate their individual behaviours to enable coherent and functional vascular network formation.

The Vascular Morphogenesis Lab has the aim to understand the molecular mechanisms regulating coordinated endothelial cell behaviour during sprouting and remodelling phases of the angiogenic process.

Research Team

Ana Figueiredo
Postdoctoral Researcher
a.figueiredo@medicina.ulisboa.pt

Ana Padilha
Postdoctoral Researcher
ana.padilha@medicina.ulisboa.pt

Andreia Pena
PhD Student
andreia.pena@medicina.ulisboa.pt

Catarina Fonseca
PhD Student
catarinafonseca@medicina.ulisboa.pt

Clara Barreto
Lab Technician
clara.barreto@medicina.ulisboa.pt

Daniela Ramalho
Lab Technician
danielaramalho@medicina.ulisboa.pt

Francisca Vasconcelos
Postdoctoral Researcher
fvasconcelos@medicina.ulisboa.pt

Hemaxi Narotamo
Lab Technician
hemaxi.narotamo@medicina.ulisboa.pt

João Manuel Coelho Carreira
PhD Student
jcarreira@medicina.ulisboa.pt

Marie Ouarné
Postdoctoral Researcher
marie.ouarne@medicina.ulisboa.pt

Marta Fidalgo
Lab Technician
martafidalgo@medicina.ulisboa.pt

Pedro Barbacena
PhD Student
pbarbacena@medicina.ulisboa.pt

Rita Rua Ferreira
Postdoctoral Researcher
ritaruaferreira@medicina.ulisboa.pt

Yulia Carvalho
Lab Technician
yulia.carvalho@medicina.ulisboa.pt

Research Areas

  • Finding novel regulators of endothelial cell migration in sprouting angiogenesis
  • Molecular regulation of endothelial cell axial polarity
  • Effects of haemodynamic forces in vascular patterning
  • Novel anti-angiogenic therapies blocking tumour angiogenesis

Ongoing Research Projects

2019/2021 ADAPT2FLOW: Adaptive and maladaptive endothelial cell dynamics. Coordinator: Marie Ourné. Funding Agency: European Commission.

2019/2020 VeCare: Selective retention of VEGF for cancer and retinopathies therapeutics. Coordinator: Cláudio Franco. Funding Agency: European Commission.

2018/2022 ATTRACT: Arterial flow as attractor for endothelial cell migration. Coordinator: Cláudio Franco. Funding Agency: Leducq Foundation.

2018/2021 Flow(in)DR: Deregulated Endothelial Blood Flow Response as a cause of Diabetic Retinopathy. Coordinator: Francisca Vasconcelos. Funding Agency: Fundação para a Ciência e a Tecnologia.

2018/2021 Invasiveless: Identify the mechanisms of endothelial tip cell invasive behavior in order to inhibit physiological and pathological sprouting angiogenesis. Coordinator: Cláudio Franco. Funding Agency: Fundação para a Ciência e a Tecnologia.

2016/2021 AXIAL.EC: Principles of Axial Polarity-Driven Vascular Patterning. Coordinator: Cláudio Franco. Funding Agency: European Commission.

Awards

  • 2018 Postdoctoral Researcher Contract - Junior Level funded by Fundação para a Ciência e Tecnologia to Francisca Vasconcelos
  • 2018 Marie Skłodowska-Curie Individual Postdoctoral Researcher Fellowship funded by the European Research Council to Marie Ouarné
  • 2013 FCT Investigator 2012 funded by Fundação para a Ciência e Tecnologia to Claudio Franco
  • 2013 Award Best Poster at Gordon Research Conferences on Angiogenesis (Newport, USA) to Claudio Franco
  • 2010 Marie Curie Intra-European Fellowship for Career Development to Claudio Franco
  • 2006 Award Best Poster at Meeting "Printemps de la Cardiologie de la Sociéte Française de Cardiologie" (Toulouse, France) to Claudio Franco

Selected Publications

- Carvalho JR, Fortunato IC, Fonseca CG, Pezzarossa A, Barbacena P, Dominguez-Cejudo MA, Vasconcelos FF, Santos NC, Carvalho FA, Franco CA. Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration. Elife. 2019 Jun 27;8. pii: e45853. doi: 10.7554/eLife.45853.

- Barbacena P, Ouarné M, Haigh JJ, Vasconcelos FF, Pezzarossa A, Franco CA. GNrep mouse: A reporter mouse for front-rear cell polarity. Genesis. 2019 Jun;57(6):e23299. doi: 10.1002/dvg.23299. Epub 2019 Apr 16.

- Hikita T, Mirzapourshafiyi F, Barbacena P, Riddell M, Pasha A, Li M, Kawamura T, Brandes RP, Hirose T, Ohno S, Gerhardt H, Matsuda M, Franco CA, Nakayama M. PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow. EMBO Rep. 2018 Sep;19(9). pii: e45253. doi: 10.15252/embr.201745253. Epub 2018 Jul 17.

- Bernabeu MO, Jones ML, Nash RW, Pezzarossa A, Coveney PV, Gerhardt H, Franco CA. PolNet: A Tool to Quantify Network-Level Cell Polarity and Blood Flow in Vascular Remodeling. Biophys J. 2018 May 8;114(9):2052-2058. doi: 10.1016/j.bpj.2018.03.032.

- Franco CA, Gerhardt H. Morph or Move? How Distinct Endothelial Cell Responses to Blood Flow Shape Vascular Networks. Dev Cell. 2017 Jun 19;41(6):574-576. doi: 10.1016/j.devcel.2017.06.008. Review.

- Franco CA, Jones ML, Bernabeu MO, Vion AC, Barbacena P, Fan J, Mathivet T, Fonseca CG, Ragab A, Yamaguchi TP, Coveney PV, Lang RA, Gerhardt H. Non-canonical Wnt signaling modulates the endothelial shear stress flow sensor in vascular remodeling. eLIFE 2016 Feb 4;5. pii: e07727.

- Wilhelm K, Happel K, Eelen G, Schoors S, Oellerich MF, Lim R, Zimmermann B, Aspalter IM, Franco CA, Boettger T, Braun T, Fruttiger M, Rajewsky K, Keller C, Brüning JC, Gerhardt H, Carmeliet P, Potente M FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature. 2016 Jan 14;529(7585):216-20.

- Franco CA, Jones M, Geudens I, Bernabeu MO, Ragab A, Collins RT, Phng LK, Coveney PV, Gerhardt H. Dynamic endothelial cell rearrangements drive developmental vessel regression. PLoS Biol 13(4):e1002125.

group leader :
Cláudio Areias Franco