Integrated Mechanistic Approaches to Cell and Regenerative Biology and Tissue/Organ-based Bioassembly
Mechanistic understanding of human organogenesis and regeneration, as well as development of artificial 3D in vitro niches for screening and disease modeling.
Cell and regenerative biology modeling
Innovative approaches are used for studying the mechanisms that affect human stem cell pluripotency, aiming at contributing to a better understanding of the molecular and cellular events that regulate stem cell function during specification of these cells into the three embryonic germ layers. Human Pluripotent Stem Cells (hPSCs) are used as model systems to establish in vitro platforms to study the cellular events involved in lineage commitment and further maturation of these cells.
Tissue and organ-based bioassembly
Exploitation of the inherent organogenic capacity of hPSCs to produce complex 3D microtissues through bioassembly. A special emphasis has been given to the production of artificial niches for neural commitment of hPSC using microencapsulation, micropatterning and microfluidics to constrain cells and generate 3D models of human cortical development. Similarly, cardiac organogenesis in 3D conditions are explored to evaluate the generation of endothelial microvessel-like structures. Hydrogel microtubes will also be used to encapsulate cells and induce definitive endoderm differentiation. This will also allow hepatic cell differentiation and maturation. Importantly, the incorporation of endothelial cells in these developmental models are useful to assess how vascularization events are processed early in human development across many different systems.
Team:
PhD holders
Tiago Fernandes, Stem cell biosystems engineering (Keywords: Pluripotent stem cells; Germ layer specification; Human organogenesis; Artificial 3D microenvironments; Innovative cell culture models)
Cláudia Miranda, Multi-organoid systems for drug screening applications (Keywords: Human pluripotent stem cells; Organoids; Body-on-a-chip; Multi-organ systems; Drug discovery)
Teresa Silva, Human pluripotent stem cell-derived cerebellar organoids (Keywords: Cerebellar development; Organoid engineering; Cerebellar ataxias; Disease modeling; Purkinje cells)
PhD students
Ana Rita Gomes, Engineering human patient-specific cerebral organoids to model Rett syndrome (Keywords: Brain development, Cerebral organoids, Rett syndrome)
André Rodrigues, 3D cellular microarray platform for human pluripotent stem cell culture and toxicology screening (Keywords: Microscale platforms, 3D cellular microenvironment, Drug screening)
Carina Maranga, Generation of 3D cerebellar organoids to model Angelman Syndrome (Keywords: Cerebellar organoids, Angelman syndrome, Disease modeling)
João Cotovio, Human liver organoids for in vitro disease modelling and drug screening (Keywords: Liver organoid, Disease modelling, Drug screening)
Master student
Maria Augusta Batista, Engineering the formation of vascular networks in human forebrain organoids (Keywords: Forebrain organoids, Vascular networks, CNS vascularization)
Key collaborators
Ana Cecília Roque (3D microtissues and hydrogel encapsulation) (FCT, UNL); Ramiro Almeida (microfluidic platforms to study cell-to-cell contacts) (UAveiro); Randolph Ashton (central nervous system development), Sean Palecek (vascularization and vascular biology), Eric Shusta (vascularization of the central nervous system) (University of Wisconsin-Madison (USA)); Jonathan Dordick (cellular microarrays for high-throughput screening) (Rensselaer Polytechnic Institute (USA)); Mohan Vemuri (scalable biomanufacturing) (R&D Director, Thermo Fisher Scientific (USA)