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ir. N.O.O. (Sander) van der Luesink

ir. N.O.O. (Sander) van der Luesink

Assistant Professor
ir. N.O.O. (Sander) van der Luesink
  • CDL Research

Research Programs

Circulatory Health

Biography

Biography

I am an assistant professor at the Central Diagnostics Laboratory which is part of the Circulatory Health Program at the University Medical Center Utrecht and University of Utrecht and work with professor dr. Gerard Pasterkamp and professor dr. Folkert W. Asselbergs. My research interest is focused on the genetic and epigenetic causes of carotid and coronary atherosclerosis underlying ischemic stroke (IS) and coronary artery disease (CAD), and their intermediate traits such as carotid intima media thickness (cIMT) and arterial calcification. Large-scale genome-wide association studies (GWAS) have identified hundreds of genetic loci robustly associated to these diseases and traits. With my work I ultimately aim to move from GWAS loci to novel therapeutic targets for cardiovascular diseases through extensive in silico, and in vitro modeling.

As a means to this end, I am currently working on integrating Bayesian fine-mapping methodology, co-localization, causal inference through Mendelian Randomization, expression and methylation quantitative trait loci analyses, GWAS, single-cell RNA sequencing, and plaque characterization based on high-throughput imaging of histological slides and machine learning algorithms. This has resulted in the identification of 28 loci with a substrate in plaques that harbor genes potentially causal to atherosclerosis and amenable to therapy. We are currently pursuing several targets in vitro.

My vision is that this holistic approach will identify the truly viable targets to feed the drug developmental pipeline to combat the cardiovascular disease epidemic. This approach is entirely human-centered and does not involved new in vivo experiments.

I actively contributed to the International Stroke Genetics Consortium. In addition, I made some contributions to international consortia, including GENIUS-CHDGIANTGLGCGoDMC, and various other international consortia.

Since 2011 I am a member of the European Atherosclerosis Society, European Society of Human Genetics, and American Society of Human Genetics. Since 2012 I am a member of the Nederlands Verenging voor Humane Genetica. Since 2017 I am a member of the European Society of Cardiology.

I hold a degree in Biology (BSc) and Medical Biology (MSc) from the Utrecht University, Utrecht, the Netherlands. I obtained my PhD in 2016 entitled "The genetics of carotid atherosclerosis - Associations with clinical outcome and histological plaque characteristics" under supervision of professor Gerard Pasterkamp, professor Paul I.W. de Bakker, and doctor Jessica van Setten.

This work is covered through various (inter)national collaborative grant programs: CVON-GENIUS2 funded by the Dutch Heart Foundation (DHF, grant-number: CVON 2017-20), ERA-CVD ‘druggable-MI-targets’ in part funded by the DHF (grant-number: JTC2017-40-2017T096), H2020 'TO_AITION', and Leducq Fondation (PlaqOmics).

Fellowship and Awards

I applied and received the following grants.

2019-09 to 2020-09SIG “DEEP-ENIGMA” | € 5,000.- | Collaborative Grant together with dr. D. Hessen, and dr. A. Bagheri.

2019-09 to 2020-09SIG “ELSIE” | in kind | Collaborative Grant together with professor dr. Aletta D. Kraneveld, professor dr. D. Oberski, and A. López-Rincón.

2019-05 to 2020-05SIG “CONVOCALS” | € 5,000.- | Collaborative Grant together with dr. A. Bagheri, and T. van de Kerkhof.

2020-01 to 2025-01: H2020 (EU) "TO_AITION" | € 473,750.- | Collaborative Grant together with professor dr. G. Pasterkamp, dr. M. Mokry, and dr. I. Höfer.

2017-09 to 2019-09: ERA-CVD JCT 2017 (EU; JTC2017-40-2017T096) “druggable-MI-genes” | € 250,000.- | Collaborative Grant together with professor dr. Folkert W. Asselbergs.

2015-06 to 2015-06: Jaap Schouten Foundation (Rotterdam, Rotterdam, Netherlands) “Travel Grant” | € 1,500.- | European Society of Human Genetics Conference 2015.

2013-2014: BBMRI-NL (Leiden, Netherlands) “Genotyping of the Abdominal Aortic Aneurysm-Express Biobank Study” | € 50,000.- | Grant number: CP2013-63.

Research Output (69)

The Applications of Single-Cell RNA Sequencing in Atherosclerotic Disease

Slenders Lotte, Tessels Daniëlle E, van der Laan Sander W, Pasterkamp Gerard, Mokry Michal 8 Feb 2022, In: Frontiers in cardiovascular medicine. 9 , p. 826103

Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis

Slenders Lotte, Landsmeer Lennart P L, Cui Kai, Depuydt Marie A C, Verwer Maarten, Mekke Joost, Timmerman Nathalie, van den Dungen Noortje A M, Kuiper Johan, de Winther Menno P J, Prange Koen H M, Ma Wei Feng, Miller Clint L, Aherrahrou Redouane, Civelek Mete, de Borst Gert J, de Kleijn Dominique P V, Asselbergs Folkert W, den Ruijter Hester M, Boltjes Arjan, Pasterkamp Gerard, van der Laan Sander W, Mokry Michal Jan 2022, In: European heart journal open. 2

The power of genetic diversity in genome-wide association studies of lipids

Graham Sarah E, Clarke Shoa L, Wu Kuan-Han H, Kanoni Stavroula, Zajac Greg J M, Ramdas Shweta, Surakka Ida, Ntalla Ioanna, Vedantam Sailaja, Winkler Thomas W, Locke Adam E, Marouli Eirini, Hwang Mi Yeong, Han Sohee, Narita Akira, Choudhury Ananyo, Bentley Amy R, Ekoru Kenneth, Verma Anurag, Trivedi Bhavi, Martin Hilary C, Hunt Karen A, Hui Qin, Klarin Derek, Zhu Xiang, Thorleifsson Gudmar, Helgadottir Anna, Gudbjartsson Daniel F, Holm Hilma, Olafsson Isleifur, Akiyama Masato, Sakaue Saori, Terao Chikashi, Kanai Masahiro, Zhou Wei, Brumpton Ben M, Rasheed Humaira, Ruotsalainen Sanni E, Havulinna Aki S, van der Laan Sander W, van Setten Jessica, de Kleijn Dominique, de Borst Gert J, Asselbergs Folkert W, Kraaijeveld Adriaan O, Beulens Joline W J, Pasterkamp Gerard, Hoefer Imo E, van der Harst Pim, Holmes Michael V, 9 Dec 2021, In: Nature. 600 , p. 675-679 5 p.

Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets

Ma Wei Feng, Hodonsky Chani J, Turner Adam W, Wong Doris, Song Yipei, Mosquera Jose Verdezoto, Ligay Alexandra V, Slenders Lotte, Gancayco Christina, Pan Huize, Barrientos Nelson B, Mai David, Alencar Gabriel F, Owsiany Katherine, Owens Gary K, Reilly Muredach P, Li Mingyao, Pasterkamp Gerard, Mokry Michal, van der Laan Sander W, Khomtchouk Bohdan B, Miller Clint L 26 Nov 2021, In: Atherosclerosis. 340 , p. 12-22 11 p.

Exploring the causal inference of shear stress associated DNA methylation in carotid plaque on cardiovascular risk

Methorst Ruben, Pasterkamp Gerard, van der Laan Sander W May 2021, In: Atherosclerosis. 325 , p. 30-37 8 p.

Common Variants Associated With OSMR Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans

van Keulen Danielle, van Koeverden Ian D, Boltjes Arjan, Princen Hans M G, van Gool Alain J, de Borst Gert J, Asselbergs Folkert W, Tempel Dennie, Pasterkamp Gerard, van der Laan Sander W 20 Apr 2021, In: Frontiers in cardiovascular medicine. 8 , p. 1-10

Monocyte-chemoattractant protein-1 levels in human atherosclerotic lesions associate with plaque vulnerability

Georgakis Marios K., van der Laan Sander W., Asare Yaw, Mekke Joost M., Haitjema Saskia, Schoneveld Arjan H., de Jager Saskia C.A., Nurmohamed Nick S., Kroon Jeffrey, Stroes Erik S.G., de Kleijn Dominique P.V., de Borst Gert J., Maegdefessel Lars, Soehnlein Oliver, Pasterkamp Gerard, Dichgans Martin 8 Apr 2021, In: Arteriosclerosis, Thrombosis, and Vascular Biology. 41 , p. 2038-2048 11 p.

Common genetic variation in mc4r does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes

Blauw Lisanne L., Noordam Raymond, van der Laan Sander W., Trompet Stella, Kooijman Sander, van Heemst Diana, Jukema Johan Wouter, van Setten Jessica, de Borst Gert J., Tybjærg-Hansen Anne, Pasterkamp Gerard, Berbée Jimmy F.P., Rensen Patrick C.N. 1 Mar 2021, In: Journal of Clinical medicine. 10 , p. 1-12 12 p.

Sex-dependent gene regulation of human atherosclerotic plaques by DNA methylation and transcriptome integration points to smooth muscle cell involvement in women

Hartman R., Siemelink M., Haitjema S., Dekkers K. F., Slenders L., Boltjes A., Mokry M., Timmerman N., De Borst G. J., Heijmans B. T., Asselbergs F. W., Pasterkamp G., Van der Laan S. W., Den Ruijter H. M. 29 Jan 2021,

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease

Demandt J A F, Dubois L J, van Kuijk K, Zaťovičová M, Jin H, Parkkila S, van der Laan S W, Jelenska L, Mees B M E, Reutelingsperger C P M, Cleutjens K B J M, van der Kallen C J H, Schalkwijk C G, van Greevenbroek M M J, Biessen E A L, Pasterkamp G, Pastoreková S, Stehouwer C D A, Sluimer J C 11 Jan 2021, In: Scientific Reports. 11 14 p.

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