RG10: Cardio-Vascular Diseases
RG10 studies myocardium and coronary vasculature development, organogenesis and function.
Main goal: to understand the etiology of Cardio-Vascular Disease (CVD) from a Developmental Biology, Genetics and Physiology perspective with Regenerative Medicine purposes.
- To investigate the signalling pathways associated with cardio-vascular diseases in collaboration with cardiologists from the Central Lisbon Hospital Centre (M Almeida and P Gonçalves). Perturbation of the Left-Right axis establishment leads to situs inversus or heterotaxy, which are frequently associated with Congenital Heart Diseases (CHDs) and linked with variants of genes involved in the Nodal and Notch pathways and/or in cilligenesis.
- To study Primary Ciliary Dyskinesia (S Lopes), in particular how Her12 signalling modulates motile/immotile cilia ratio leading to Cerl2/Dand5 expression defects, which is a key molecule in the modulation of Nodal activity. Cerl2 KO mice display cardiac hyperplasia and a variant for the human Cerl2/Dand5 gene has been identified in patients with CHD. Previously generated iPS cells from these patients will be used for regenerative medicine and disease modelling purposes (J Belo).
- To study the role of CCBE1 in cardiomyocyte formation and in the generation of the coronary vasculature (J Belo).
- Atherosclerosis is a major cause of CVD. Understanding the molecular and cellular interactions that lead to atherosclerotic plaque formation and progression will lead to novel biomarkers, early detection of subclinical disease, choice of therapy, and novel therapeutic approaches. The group is addressing these issues by identifying novel biomarkers based on shotgun lipidomic profiles of plasma of CVD patients, and defining new paradigms in the pathogenesis of atherosclerosis to uncover new druggable targets, in particular lysosome dysfunction (O Vieira).
Keywords: Atherosclerosis; Congenital Heart Diseases; Primary Ciliary Dyskinesia; Cholesteryl hemiesters
Bover O, Justo T, Pereira PNG, Facucho-Oliveira J, Inácio JM, Ramalho JS, Domian IJ, Belo JA (2018) Loss of Ccbe1 affects cardiac-specification and cardiomyocyte differentiation in mouse embryonic stem cells. PLoS One 13(10):e0205108
Gibson M, Domingues N, Vieira OV (2018) Lipid and non-lipid factors affecting macrophage dysfunction and inflammation in atherosclerosis. Frontiers in Physiology 9:654
Silva MM, Gomes-Alves P, Rosa S, Simão D, Inácio JM, Peixoto C, Serra M, Belo JA, Alves PM (2018) Full-length human CCBE1 production and purification: leveraging bioprocess development for high quality glycosylation attributes and functionality. Journal of Biotechnology 285:6-14
Bonet F, Pereira PNG, Bover O, Marques S, Inácio JM, Belo JA (2018) CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart. Developmental Dynamics 247(10):1135-1145
Pars S, Cristo F, Inácio JM, Rosas G, Carreira IM, Melo JB, Almeida LP, Mendes P, Martins DS, Maio J, Anjos R, Belo JA (2018) Generation and characterization of a human iPS cell line from a patient-related control to study disease mechanisms associated with DAND5 p.R152H alteration. Stem Cell Research 29:202-206