European projects funded by the Marie Skłodowska-Curie Actions program
Personalized medicine for the treatment of gastrointestinal cancers, treatment of bone pain and the study of glycans in the processes of tumor progression and proliferation are the themes of the three European projects which the Institute for Research and Innovation in Health of the University of Porto (i3S) are involved and which were recently funded by the European Union program Marie Skłodowska-Curie Actions (MSCA) - which aims to promote research excellence and graduate and postgraduate training of researchers.
These projects total around one million euros for i3S and will allow their coordinators, Celso Reis, Cristina Barrias, and Meriem Lamghari, to select four non-resident students in Portugal who will then be enrolled at the University of Porto. During a period of three years, there will be a rotation of the training sites, which means that the i3S teams will receive and train students from the other partners of the respective consortia and their students will also do part of their PhD in partner institutions.
New in vitro models that mimic human organs of the gastrointestinal tract
The TOP-GUT European project aims to train PhD students in the area of innovative preclinical models for the advancement of personalized medicine in gastrointestinal tract cancers. The project involves eight partners, of which six are academic, and has the Portuguese participation of i3S researchers Celso Reis, leader of the Glycobiology in Cancer group, and Cristina Barrias, who leads the Bioengineered 3D Microenvironments group.
“We are going to make new in vitro models capable of mimicking human organs of the gastrointestinal tract and develop new tools and protocols to create more complex gastrointestinal models, namely using advanced ‘organ-on-chip’ technology. This means that we will have new models for personalized medicine using organoids derived from patients”, explains Celso Reis.
At the i3S the PhD student under the guidance of researchers Cristina Barrias and Marta Silva will develop an “organ-on-chip” platform designed to simulate the in vivo microenvironment, which will then be used to investigate the impact of stromal components, namely fibroblasts, microvasculature and extracellular matrix, in the development and function of gastric and intestinal organoids.
The PhD student, who will be supervised by Celso Reis and Filipe Pinto, will develop and characterize human gastric organoids to study oncogenic receptors, “immuno checkpoints” and evaluate the impact of glycosylation on these targets through studies of glycomics and proteomics. “The effects of specific drugs on organoids will also be studied and their effect compared with the respective primary tumor to assess their impact on personalized medicine”, explains Celso Reis.
Musculoskeletal pain: advance to the clinical phase
Led by Meriem Lamghari, BonePain III follows in the footsteps of its predecessors, BonePain I and II, which focused on the study of musculoskeletal pain caused by diseases such as arthritis and bone cancer, and aims to advance towards a more clinical stage. In this project, explains the researcher, “12 European partners (from academia and industry) join forces to create an exceptional integrated training program for researchers at the beginning of their careers, with the aim of increasing the capacity for clinical translation of bone pain research, the drug discovery and provide new mechanistic insight and potential therapeutic targets to a new generation of scientists”.
The Portuguese team will develop fully humanized “organ-on-a chip” models of the bone disease microenvironment to obtain clinically relevant data. The consortium, adds Meriem Lamghari, “intends to identify new disease mechanisms, potential treatment targets and explore the effectiveness of therapies in painful skeletal diseases, such as osteoarthritis, rheumatoid arthritis, bone cancer, rare bone disease or fibrous dysplasia”.
“In an extensive training effort that covers both specific research skills and transferable skills, selected students will obtain excellent and innovative interdisciplinary training from all partners. Students will benefit from training with industrial partners and with some of the main researchers specializing in pain in Europe”, underlines the researcher.
Stop tumor cells by attacking the glycans
The European project GlyCanDrug, for its part, focuses on the development of new precision therapeutic strategies targeting glycosylation in cancer. In this European network, whose Portuguese participation is led by researcher Celso Reis, nine European partners are involved, each of which are outstanding in academia and industry.
Under the guidance of researchers Celso Reis, Joana Gomes and Catarina Gomes, strategies will be developed to precisely modulate the expression of glycans expressed by tumor cells. “The focus will be directed to the most important glycans in the processes of tumor progression and proliferation, we will use highly specific and cutting-edge inhibitors that interfere in the biosynthesis and in the functional interaction of these glycans in a biological context”, explains Celso Reis.
The team also intends to develop and evaluate antibodies directed to cancer-specific glycan epitopes. This strategy assures the researcher “will contribute to the discovery and application of new formulas and treatments in a context of precision medicine”.