Systems Biology of Vascular Disease
Research Topics uitklapper, klik om te openen
Our research utilizes the largest biobank of well-characterized atherosclerotic plaques with more than 4000 included patients – the Athero-Express study. We generate various types of complex “-omics” datasets, including genotyping, transcriptomics (bulk, single-cell and spatially resolved), DNA methylation (bulk and single-cell) and proteomics. These datasets are integrated with histological and clinical data to unravel mechanisms in plaque pathogenesis and allow us to identify specific processes that lead to the severe manifestation of atherosclerotic disease like stroke and myocardial infarction. Next to computational tools, we use primary in vitro model systems derived from vascular and plaque cells and molecular biology techniques for validation and mechanistic studies.
Key Publications uitklapper, klik om te openen
Robin J.G. Hartman, Katie Owsiany, Lijiang Ma, Simon Koplev, Ke Hao, Lotte Slenders, Mete Civelek, Michal Mokry, Jason C. Kovacic, Gerard Pasterkamp, Gary Owens, Johan L.M. Björkegren, Hester M. den Ruijter. Sex-Stratified Gene Regulatory Networks Reveal Female Key Driver Genes of Atherosclerosis Involved in Smooth Muscle Cell Phenotype Switching. Circulation. 2021 Feb 16;143(7):713-726. doi: 10.1161/CIRCULATIONAHA.120.051231
Depuydt MAC, Prange KHM, Slenders L, Örd T, Elbersen D, Boltjes A, de Jager SCA, Asselbergs FW, de Borst GJ, Aavik E, Lönnberg T, Lutgens E, Glass CK, den Ruijter HM, Kaikkonen MU, Bot I, Slütter B, van der Laan SW, Yla-Herttuala S, *Mokry M, *Kuiper J, *de Winther MPJ, *Pasterkamp G. Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics. Circulation Research 2020. https://doi.org/10.1161/CIRCRESAHA.120.316770
Siemelink MA, van der Laan SW, Haitjema S, van Koeverden ID, Schaap J, Wesseling M, de Jager SCA, Mokry M, van Iterson M, Dekkers KF, Luijk R, Foroughi Asl H, Michoel T, Björkegren JLM, Aavik E, Ylä-Herttuala S, de Borst GJ, Asselbergs FW, El Azzouzi H, den Ruijter HM, Heijmans BT, Pasterkamp G. Smoking is Associated to DNA Methylation in Atherosclerotic Carotid Lesions. Circ Genom Precis Med. 2018 Sep;11(9):e002030. doi: 10.1161/CIRCGEN.117.002030.
Haitjema S, Meddens CA, van der Laan SW, Kofink D, Harakalova M, Tragante V, Foroughi Asl H, van Setten J, Brandt MM, Bis JC, O'Donnell C, Cheng C, Hoefer IE, Waltenberger J, Biessen E, Jukema JW, Doevendans PA, Nieuwenhuis EE, Erdmann J, Björkegren JL, Pasterkamp G, Asselbergs FW, den Ruijter HM, Mokry M. Additional Candidate Genes for Human Atherosclerotic Disease Identified Through Annotation Based on Chromatin Organization. Circ Cardiovasc Genet. 2017 Apr;10(2):e001664. doi: 10.1161/CIRCGENETICS.116.001664. PMID: 28320757
Guus W. van Lammeren, Hester M. den Ruijter, Joyce E. P. Vrijenhoek, Sander W. van der Laan, Evelyn Velema, Jean-Paul P. M. de Vries, Dominique P. V. de Kleijn, Aryan Vink, Gert Jan de Borst, Frans L. Moll, Michiel L. Bots, and Gerard Pasterkamp. Time-dependent changes in atherosclerotic plaque composition in patients undergoing carotid surgery. Circulation 2014;129:2269-76.
People Involved uitklapper, klik om te openen
Contact uitklapper, klik om te openen
Michal Mokry
Gerard Pasterkamp