Cláudio Franco Lab

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

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.

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

Fidalgo MF, Fonseca CG, Caldas P, Raposo AA, Balboni T, Henao-Mišíková L, Grosso AR, Vasconcelos FF, Franco CA. Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes. Life Sci Alliance. 2022 Oct 11;5(12):e202201554. doi: 10.26508/lsa.202201554.

Barbacena P, Dominguez-Cejudo M, Fonseca CG, Gómez-González M, Faure LM, Zarkada G, Pena A, Pezzarossa A, Ramalho D, Giarratano Y, Ouarné M, Barata D, Fortunato IC, Misikova LH, Mauldin I, Carvalho Y, Trepat X, Roca-Cusachs P, Eichmann A, Bernabeu MO, Franco CA. Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina. Dev Cell. 2022 Oct 10;57(19):2321-2333.e9. doi: 10.1016/j.devcel.2022.09.002.

Narotamo H, Ouarne M, Franco CA, Silveira M. Synthetic Generation of 3D Microscopy Images using Generative Adversarial Networks. Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:549-552. doi: 10.1109/EMBC48229.2022.9871631.

Janota CS, Pinto A, Pezzarossa A, Machado P, Costa J, Campinho P, Franco CA, Gomes ER. Shielding of actin by the endoplasmic reticulum impacts nuclear positioning. Nat Commun. 2022 May 19;13(1):2763. doi: 10.1038/s41467-022-30388-3.

De Niz M, Brás D, Ouarné M, Pedro M, Nascimento AM, Henao Misikova L, Franco CA, Figueiredo LM. Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence. Cell Rep. 2021 Sep 21;36(12):109741. doi: 10.1016/j.celrep.2021.109741.

Park H, Furtado J, Poulet M, Chung M, Yun S, Lee S, Sessa WC, Franco CA, Schwartz MA, Eichmann A. Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. Circulation. 2021 Sep 7;144(10):805-822. doi: 10.1161/CIRCULATIONAHA.120.053047. Epub 2021 Jun 29.

Figueiredo AM, Barbacena P, Russo A, Vaccaro S, Ramalho D, Pena A, Lima AP, Ferreira RR, Fidalgo MA, El-Marjou F, Carvalho Y, Vasconcelos FF, Lennon-Duménil AM, Vignjevic DM, Franco CA. Endothelial cell invasion is controlled by dactylopodia. Proc Natl Acad Sci USA. 2021 May 4;118(18):e2023829118. doi: 10.1073/pnas.2023829118.

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.

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, 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.

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.