Molecular determinants of granuloma formation in lung disease

Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology with lung involvement in most cases. The pathological hallmark of sarcoidosis is the formation of non-necrotizing granulomas incited by the accumulation of activated macrophages and T-cells, and the local production of proinflammatory cytokines. Despite their clinical significance to sarcoidosis, the molecular and cellular sequences of events promoting macrophage aggregation and transformation into epithelioid cells that initiate and maintain granulomas remain elusive. We aim to elucidate the molecular mechanisms that activate and regulate granuloma formation in sarcoidosis, by resorting to a translational approach combining cutting-edge research tools, advanced preclinical cellular and animal models, and human patients. In particular, we propose to resolve the immunometabolic signatures that drive granuloma formation, define the contribution of metabolic profiles to immune cell function during granulomatous inflammation; and map novel immunometabolic candidates of genetic susceptibility to sarcoidosis. We expect thus to reveal essential pathogenetic mechanisms underlying granulomatous inflammation, and identify new therapeutic solutions for sarcoidosis.

Funding Agency

Fundação para a Ciência e a Tecnologia

Project Reference

PTDC/MED-OUT/1112/2021

Project Members

Main Project Outcomes

S. Queirós, “Right ventricular segmentation in multi-view cardiac MRI using a unified U-net model”, in E. Puyol Antón et al. (eds) Statistical Atlases and Computational Models of the Heart. Multi-Disease, Multi-View, and Multi-Center Right Ventricular Segmentation in Cardiac MRI Challenge. STACOM 2021. Lecture Notes in Computer Science, vol 13131, pp. 287-295, Springer, Cham, 2022.

“Best Paper Award in the M&Ms-2 Challenge”, by M&Ms2 Challenge organizers and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society.