Towards therapeutics for vascular calcification: Calcification-Omics, Molecular Elucidation, & Therapeutics (COMET) Network
The Duer group is part of a research collaboration project funded by the Leducq Foundation that will begin January 2025. The project will exploit recent advances in patient genomics, proteomics and metabolomics and biophysical methods to fully characterize the calcifcation deposits from patient arteries to work out molecular mechanisms of vascular calcification that occur in patients, and then how to inhibit those mechanisms. Expect regular updates on this webpage on the progress of the project from January 2025...
The project partners are:
Professor Rajeev Malhotra (Massachusetts General Hospital and Harvard Medical School) - North American coordinator
Professor Catherine Shanahan (Kings College London) - European coordinator
Professor Clint L. Miller (Center for Public Health Genomics, University of Virginia)
Professor Yabing Chen (Oregon Health and Science University)
Professor Melinda J. Duer (University of Cambridge)
Professor Maryam Kavousi (Erasmus MC, University Medical Center Rotterdam)
Professor Rafael Kramann (RWTH Aachen University)
Vascular calcification is a global health issue contributing to a multitude of cardiovascular diseases including atherosclerotic cardiovascular disease, arterial stiffness with associated hypertensive heart disease, and calciphylaxis. There is no targeted therapy for vascular calcification, which is becoming increasingly prevalent due to the ageing population and increases in worldwide cases of diabetes and chronic kidney disease. Smooth muscle cells (SMCs) are central players in orchestrating the calcification process which is regulated by both biological and physicochemical pathways. Key mechanisms of calcification including loss of inhibitors, osteogenic differentiation and mineral nidus formation and metabolic stress and ageing are key drivers of these processes. Despite these advances in mechanistic understanding, the development of therapeutics now requires further detailed knowledge of (1) culprit SMC populations in different disease contexts, (2) identification of new candidates to target and (3) how cross-talk between ageing SMCs and the ageing extracellular matrix (ECM) environment in the vascular niche impacts cell phenotype and nidus formation. With these aims in mind this network will focus on the function of newly identified genetic and multi-omic targets for calcification, use transcriptomics to dissect SMC heterogeneity and signalling pathways in the calcification niche and apply chemistry and proteomics approaches to understand ECM modifications and how they impact on physicochemical properties of mineralization. These data will feed into candidate and AI-based therapeutic approaches aimed at modulating calcification in rare genetic conditions and the general population.