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Janine van Gils, PhD

My research interest is the role of neuronal guidance cues in inflammation and vascular biology. Despite significant therapeutic advancements, cardiovascular disease persists to be a worldwide leader of morbidity and mortality. Atherosclerosis, a main driver of cardiovascular disease, progresses following the transmigration of lipids and inflammatory cells through the vascular endothelium into the vascular wall.

The ligands and receptors of the Neuronal Guidance Cues (NGCs) are emerging as significant regulators of inflammation. As a post-doc in the in the lab of Prof. K.J. Moore at Harvard Medical School and New York University I received an excellent training in atherosclerosis biology and gained the foundation for my vast interest and knowledge on neuronal guidance cues. A personal fellowship from the American Heart Association allowed me to demonstrate that the NGC netrin-1 is highly expressed and secreted by macrophages and promotes atherosclerosis by inhibiting the emigration of macrophages from the plaques. A paper describing this work, that was published in Nature immunology (van Gils et al. Nat Immunol. 2012), received international interest and was awarded the Vascular Biology Award in 2012. In subsequent studies, we provided evidence that several NGCs may also be involved in the adhesion of leukocytes to endothelial cells and the subsequent migration of leukocytes into the subendothelial space.

Supported by a personal grant from the Dutch Heart Foundation I could establish my own research line on NGCs and atherosclerosis in the Einthoven Laboratory, additionally supported by a Rembrandt Institute on Cardiovascular Science Award. My goal is to acquire a deeper insight into the role of NGCs in atherosclerosis and take the next step towards translation and assess the clinical relevance in patients with coronary artery disease.

Key publications
– Ramkhelawon B et al. Hypoxia induces netrin-1 and Unc5b in atherosclerotic plaques: mechanism for macrophage retention and survival. Arteriosclerosis Thrombosis and Vascular Biology. 2013; 33:1180-8. Pubmed
– Wanschel A et al. The neuroimmune guidance cue, semaphorin3E, is expressed in mouse atherosclerotic plaques and negatively regulates macrophage migration. Arteriosclerosis Thrombosis and Vascular Biology. 2013; 33:886-93. Pubmed
– Van Gils JM and Ramkhelawon B et al. Endothelial expression of guidance cues in vessel wall homeostasis: Dysregulation in pro-atherosclerotic conditions. Arteriosclerosis Thrombosis and Vascular Biology. 2013; 33:911-9. Pubmed
– Van Gils JM et al. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nature Immunology. 2012; 13:136-43. Pubmed

See full publication list here