- 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]
- Zhou Fangfang, Drabsch Yvette, Dekker Tim J. A., de Vinuesa Amaya Garcia, Li Yihao, Hawinkels Lukas J. A. C., Sheppard Kelly-Ann, Goumans Marie-José, Luwor Rodney B., de Vries Carlie J., Mesker Wilma E., Tollenaar Rob A. E. M., Devilee Peter, Lu Chris X., Zhu Hongjian, Zhang Long, Dijke Peter Ten Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling Nature communications 2014;5:3388-(13 p.) [PubMed]
- Kurakula Kondababu, Sommer Daniela, Sokolovic Milka, Moerland Perry D., Scheij Saskia, van Loenen Pieter B., Koenis Duco S., Zelcer Noam, van Tiel Claudia M., de Vries Carlie J. M. LIM-Only Protein FHL2 Is a Positive Regulator of Liver X Receptors in Smooth Muscle Cells Involved in Lipid Homeostasis Molecular and cellular biology 2015;35 (1):52-62 [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]
Prof. PhD C.J.M. de Vries (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.
Theme: Cardiovascular Diseases
PhD T.W.H. Pols
BSc P.B. van Loenen
BSc M. Vos
- AMC (Vrijgesteld)
- UniQure Biopharma BV