Projects per year
Personal profile
Research interests
My main interest is the transcriptional regulation of myeloid cells in health and disease. Myeloid cell differentiation is a fascinatingly plastic procedure, where unstimulated cells morph into highly specialized phenotypes. Dysregulation of this process gives rise to various diseases and syndromes, such as myeloid leukemia, atherosclerosis, rheumatoid arthritis, and bacterial sepsis.
During my graduate training, I worked on the molecular and epigenetic mechanisms behind certain genomic translocation induced forms of acute myeloid leukemia, such as MLL-AF9 and AML-ETO positive leukemias.
My current line of research excitingly combines fundamental macrophage biology -i.e., the interesting mechanisms behind switching of macrophage activation states at the molecular level- with clinically highly relevant diseases like atherosclerosis.
Macrophage activation is hallmarked by the sequential opening up of chromatin by signal dependent transcription factors which target gene programs for specific activation states (e.g., inflammatory or fibrotic.) Specialized macrophages are primed for transcription of response genes by epigenetic processes like DNA methylation and histone modification, and subsequent RNA-polymerase II promoter stalling.
I am highly interested in this epigenetic component of transcriptional regulation of macrophages, and myeloid cells in general. In order to investigate these processes, I like to deploy genomics and transcriptomics assays such as ChIP- ATAC, and RNA-seq, on a bulk or single-cell level. I am skilled at the execution of these genomewide assays, and adept at analyzing the big data sets they generate. I highly enjoy the computational biology groundwork -coding-, as well as the piecing together of the biological puzzle this entails.
specialisation
Wet Lab:
- Genomewide assays
- ChIP-seq
- ATAC-seq
- (sc)RNA-seq
- CROP-seq
- Mol Bio
- CRISPR KO / OE
- Cloning
- Viral transduction
- Transfection
- CRISPR screen library generation
Computational Biology
- Analyses of genomewide assays
- ChIP-seq
- ATAC-seq
- RNA-seq
- Single sell ATAC- and RNA-seq
- CROP-seq
- Tools
- R
- e.g. DEseq2, Seurat, MUSIC
- Homebrew package development
- Python
- e.g. gimme motifs, fluff, velocyto
- Bash
- e.g. HISAT2, MACS2, HOMER
- Homebrew pipeline development for mapping, peak calling, etc.
- SLURM
- Homebrew pipeline development for automated processing of samples on a super cluster.
- GIT
- All code deposited and version controlled for reproducibility
- Renv and conda package management
- R
Education/Academic qualification
PhD, The Epigenetic landscape of genomic translocation induced Acute Myeloid Leukemia, Radboud Universiteit Nijmegen
1 May 2011 → 30 Sept 2016
Award Date: 29 Jun 2017
Keywords
- Q Science (General)
- bioinformatics
- computational biology
- epigenetics
- transcriptional regulation
- R
- Python
- bash
- translocation
- genomics
- transcriptomics
- genetics
- single cell
- chromatin
- histone
- myeloid
- monocyte
- macrophage
- R Medicine (General)
- atherosclerosis
- foam cell
- plaque
- endarterectomy
- leukemia
- inflammation
Collaborations and top research areas from the last five years
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Epigenetic and transcriptional regulation of macrophages in atherosclerosis and CVD
1/10/2016 → …
Project: Research
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Epigenetic and transcriptional regulation of macrophages in acute myeloid leukemia
1/05/2011 → 1/02/2019
Project: Research
Research output
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Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation
Dzobo, K. E., Cupido, A. J., Mol, B. M., Stiekema, L. C. A., Versloot, M., Winkelmeijer, M., Peter, J., Pennekamp, A-M., Havik, S. R., Vaz, F. M., van Weeghel, M., Prange, K. H. M., Levels, J. H. M., de Winther, M. P. J., Tsimikas, S., Groen, A. K., Stroes, E. S. G., de Kleijn, D. P. V. & Kroon, J., 1 Mar 2024, In: Arteriosclerosis, Thrombosis, and Vascular Biology. 44, 3, p. 720-740 21 p.Research output: Contribution to journal › Article › Academic › peer-review
Open Access -
Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques
Benavente, E. D., Karnewar, S., Buono, M., Mili, E., Hartman, R. J. G., Kapteijn, D., Slenders, L., Daniels, M., Aherrahrou, R., Reinberger, T., Mol, B. M., de Borst, G. J., de Kleijn, D. P. V., Prange, K. H. M., Depuydt, M. A. C., de Winther, M. P. J., Kuiper, J., Bj Rkegren, J. L. M., Erdmann, J., Civelek, M., & 4 others , 9 Feb 2023, In: bioRxiv.Research output: Contribution to journal › Article › Academic › peer-review
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Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation
Ninni, S., Dombrowicz, D., Kuznetsova, T., Vicario, R., Gao, V., Molendi-Coste, O., Haas, J., Woitrain, E., Coisne, A., Neele, A. E., Prange, K., Willemsen, L., Aghezzaf, S., Fragkogianni, S., Tazibet, A., Pineau, L., White, J. R., Eeckhoute, J., Koussa, M., Dubrulle, H., & 8 others , 4 Apr 2023, In: Journal of the American College of Cardiology. 81, 13, p. 1263-1278 16 p.Research output: Contribution to journal › Article › Academic › peer-review
8 Citations (Scopus) -
Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells
Depuydt, M. A. C., Schaftenaar, F. H., Prange, K. H. M., Boltjes, A., Hemme, E., Delfos, L., de Mol, J., de Jong, M. J. M., Bernabé Kleijn, M. N. A., Peeters, J. A. H. M., Goncalves, L., Wezel, A., Smeets, H. J., de Borst, G. J., Foks, A. C., Pasterkamp, G., de Winther, M. P. J., Kuiper, J., Bot, I. & Slütter, B., 1 Feb 2023, In: Nature cardiovascular research. 2, 2, p. 112-125 14 p.Research output: Contribution to journal › Article › Academic › peer-review
Open Access19 Citations (Scopus) -
Sterol-regulated transmembrane protein TMEM86a couples LXR signaling to regulation of lysoplasmalogens in macrophages
van Wouw, S. A. E., van den Berg, M., el Ouraoui, M., Meurs, A., Kingma, J., Ottenhoff, R., Loix, M., Hoeksema, M. A., Prange, K., Pasterkamp, G., Hendriks, J. J. A., Bogie, J. F. J., van Klinken, J. B., Vaz, F. M., Jongejan, A., de Winther, M. P. J. & Zelcer, N., 1 Feb 2023, In: Journal of Lipid Research. 64, 2, p. 100325 1 p., 100325.Research output: Contribution to journal › Article › Academic › peer-review
Open Access1 Citation (Scopus)
Datasets
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Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics
Slenders, L. (Creator), Van Der Laan, S. W. (Creator), Mokry, M. (Creator), Depuydt, M. A. C. (Creator), Boltjes, A. (Creator), Asselbergs, F. (Creator), Pasterkamp, G. (Creator), Prange, K. (Creator), Örd, T. (Creator), Elbersen, D. (Creator), De Jager, S. C. A. (Creator), De Borst, G. J. (Creator), Aavik, E. (Creator), Lönnberg, T. (Creator), Lutgens, E. (Creator), Glass, C. K. (Creator), Ruijter, H. M. D. (Creator), Kaikkonen, M. U. (Creator), Bot, I. (Creator), Slütter, B. (Creator), Yla-Herttuala, S. (Creator), Kuiper, J. (Creator) & de Winther, M. (Creator), DataverseNL, 2022
DOI: 10.34894/rwahls, https://dataverse.nl/citation?persistentId=doi:10.34894/RWAHLS
Dataset