- Koenis Duco Steven, Medzikovic Lejla, van Loenen Pieter Bas, van Weeghel Michel, Huveneers Stephan, Vos Mariska, Evers-van Gogh Ingrid Johanna, van den Bossche Jan, Speijer Dave, Kim Yongsoo, Wessels Lodewyk, Zelcer Noam, Zwart Wilbert, Kalkhoven Eric, de Vries Carlie Jacoba Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism Cell reports 2018;24 (8):2127-2140.e7 [PubMed]
- Koenis Duco S., Medzikovic Lejla, Vos Mariska, Beldman Thijs J., van Loenen Pieter B., van Tiel Claudia M., Hamers Anouk A. J., Rubio Iker Otermin, de Waard Vivian, de Vries Carlie J. M. Nur77 variants solely comprising the amino-terminal domain activate hypoxia-inducible factor-1 α and affect bone marrow homeostasis in mice and humans Journal of biological chemistry 2018;293 (39):15070-15083 [PubMed]
- Kurakula Kondababu, Koenis Duco S., van Tiel Claudia M., de Vries Carlie J. M. NR4A nuclear receptors are orphans but not lonesome BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2014;1843 (11):2543-2555 [PubMed]
- Kurakula K., Vos M., Logiantara A., Roelofs J. J. T. H., Nieuwenhuis M. A., Koppelman G. H., Postma D. S., Brandsma C. A., Sin D. D., Bossé Y., Nickle D. C., van Rijt L. S., de Vries C. J. M. Deficiency of FHL2 attenuates airway inflammation in mice and genetic variation associates with human bronchial hyper-responsiveness Allergy 2015;70 (12):1531-1544 [PubMed]
- Hamers Anouk A. J., Vos Mariska, Rassam Fadi, Marincovic Goran, Kurakula Kondababu, van Gorp Patrick J., de Winther Menno P. J., Gijbels Marion J. J., de Waard Vivian, de Vries Carlie J. M. Bone Marrow-Specific Deficiency of Nuclear Receptor Nur77 Enhances Atherosclerosis Circulation research 2012;110 (3):428-U147 [PubMed]
Carlie de Vries was trained as a molecular biologist at the University of Utrecht after which she worked on her thesis at Sanquin Laboratories (Amsterdam). She did a postdoc at the University of California San Francisco, where she cloned the first VEGF-receptor with a fellowship from the Netherlands Organisation for Scientific Research (NWO), followed by a postdoc at the Hubrecht Institute in Utrecht studying ActivinA in zebrafish. After this, the department of Medical Biochemistry at the AMC hired her within the ‘Molecular Cardiology Program' supported by the Netherlands Heart Foundation involving an Established Investigator-ship (2002). Since 2008 De Vries is full professor at the University of Amsterdam, she is heading the department as of 2014 and is chair of the Board of the AMC Graduate School of Medical Sciences (over 1700 PhD candidates). Carlie’s research focuses on the role of the nuclear receptor Nur77 and its coregulator FHL2 in cardiovascular and metabolic diseases and is funded by The Netherlands Heart Foundation, NWO and Amsterdam Cardiovascular Sciences.
Prof. C.J.M. de Vries PhD (Regulation of Vascular Homeostasis and Metabolism)
The research of Carlie de Vries aims to dissect the molecular processes underlying the function of the nuclear receptor Nur77, which is known to modulate metabolism and for which she has demonstrated that it inhibits atherosclerosis. The research program has a strong focus on macrophages, cardiomyocytes, smooth muscle cells and endothelial cells. ChIPseq/RNAseq studies in macrophages have been performed to delineate the downstream signaling of Nur77. Nur77 indeed modulates the expression of genes involved in metabolic pathways and inflammatory processes. So far, no ligands have been identified binding the traditional pocket in the ligand-binding domain, however in silico searches for small-molecule interactions revealed potential alternative binding sites for specific drugs. Dedicated mouse models are operational and allow verification of in vitro observations towards translation in clinical practice.
The activity of Nur77 is regulated by interacting proteins that were identified, such as the peptidyl-prolyl isomerase Pin1 and the LIM-domain only protein FHL2. Follow up studies on FHL2 revealed that this protein is functionally involved in inhibition of smooth muscle proliferation and that FHL2 deficiency attenuates airway inflammation in mice. Moreover, genetic variation in the FHL2 gene associates with human bronchial hyper-responsiveness.
Currently, we are studying the role of FHL2 in type 2 diabetes in \FHL2-deficient mice.
Theme: Cardiovascular Diseases
J. van den Burg
M. Vos BSc
- AMC (Vrijgesteld)
- UniQure Biopharma BV