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Projects

Current research projects

The role of arginine methylation in erythroid development: 
  Arginine methylation is a crucial post-translational modification regulating protein-protein interactions. It is implicated in the regulation of chromatin dynamics, transcription, signal transduction, and RNA processing. We study the role of the of Prmt1, the predominant Protein Arginine Methyl Transferase, in erythroid transcriptional regulation by: (1) identification of Prmt1 binding partners, (2) expression profiling of cells that over/under-express Prmt1 and/or binding partners, and (3) knock down experiments in zebrafish embryos.
Thamar van Dijk, Pavlos Fanis and Sylvia Dekker

Purification of hematopoietic transcription factor complexes:
  While Gata1 is a key regulator of erythroid cell differentiation, Gata2 plays an essential role in the proliferation and survival of hematopoietic progenitor and stem cells. Gata2 can rescue the lethal phenotype of Gata1 deficient mice to a certain degree, showing, in addition to their unique functions, the potential of GATA factors to substitute each other in some processes. We are trying to elucidate differences and redundancy of functions by the identification and characterization of multi-protein complexes formed by Gata2 and other hematopoietic transcription factors.
Harald Braun

Transcription factors in erythropoiesis:
   I am interested in the role of transcription factors belonging to the GATA and Sp/XKLF family, and particularly in their role in erythropoiesis. For this study I make use of genetically modified mice, either conditional knockouts or transgenics.
Nynke Gillemans.
REDS signaling and terminal erythroid differentiation:
   The erythroblastic island is the entity where definitive erythropoiesis occurs in the fetal and adult stages in mammals. Red cell differentiation signal (REDS) is a homotypic signaling mechanism that occurs between erythroid cells in the erythroblastic island. We hypothesize that REDS is produced by mature erythroid cells and instructs less mature erythroid cells to undergo terminal erythroid differentiation. This mechanism contributes to the homeostasis of erythropoiesis. We are currently dissecting the molecular mechanism of REDS action using proteomics, transgenic mice and zebrafish.
Dendritic cells:
We are studying the role of Gata1 in the development and function of dendritic cells. Gata1 is expressed in this haematopoietic lineage and is required for the survival of dendritic cells and their response to stress stimuli, i.e. inflammatory responses.
Laura Gutiérrez, Sahar Esteghamat and Teus van Gent
Gene expression profile in lung cancer:
   Lung cancers are among the most prevalent cancers in the human population, with very poor prognosis for the patients. Most of lung cancers are diagnosed when the disease is already at an advanced stage when treatments such as surgical removal and chemotherapy have little or no therapeutic effect. It would therefore be highly desirable to develop a set of molecular markers that enable early detection of lung cancers in the groups at risk.
We are therefore performing a study of gene expression profiles in lung cancers. We use surgically removed lung samples from patients with full clinical description and follow-up. These samples are used to perform a genome-wide gene expression analysis on Affymetrix GeneChip® Human Genome U133 Plus 2.0 arrays.
With the microarray data, we are building a data set that will be used to define a set of predictor genes. This will ultimately result in a set of gene signatures that can be used for prognostic and diagnostic purposes, and for the discovery of new therapeutic targets.
Jun Hou and Rejane Hughes
  The role of SP factors in C. elegans:
   Regulation of transcription is an important mechanism involved in the process of application of genetic information contained in the DNA sequence in every particular cell. Among such regulators belong also the SP (specificity protein) transcriptional factors. We have knowledge on the involvement of the SP factors in various processes from mice knockout phenotypes as well as from clinical medicine, but there is still need for the further characterisation of their particular functions. Based on phylogenetic analysis there have been 3 SP-related factors characterised in the nematode Caenorhabditis elegans. C.elegans as a model organism provides us with vast knowledge of its development, all the cell lineages, cell functions and with many genetic advantages and is therefore suitable for our studies of the biological roles of these transcriptional factors.
Eva Krpelanova