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University Medical Center Groningen

Department of Experimental Hematology

labretreat
labretreat

The general aims of the division of Experimental Hematology are to obtain detailed knowledge on (molecular) mechanisms that determine hematopoietic stem cell self-renewal and differentiation, with the ultimate goal to deepen our insights in the development of human leukemias. We have a specific interest in dissecting the clonal heterogeneity of leukemias and recently developed tools that allow us to identify and prospectively isolate genetically distinct clones within individual patients. We perform gene-function analyses in human hematopoietic stem and progenitor cells isolated from cordblood and bone marrow utilizing various strategies including optimized retro/lentiviral transduction protocols and inducible RNAi and CRISPR/Cas9 approaches. We have a longstanding expertise in using molecular approaches (transcriptome, proteome and epigenome) to further understand processes such as hematopoietic differentiation, proliferation, apoptosis and self-renewal. We utilize a series of cell biological in vitro and in vivo model systems to be able to translate knowledge from our molecular research lines to more general concepts of hematopoietic stem cell biology. We make use of sophisticated humanize niche xenograft models in order to mimic that situation in leukemia patients as closely as possible. Furthermore, we directly collaborate with the clinical and diagnostic departments at the UMCG and have banked large series of leukemic patient material and are currently focusing on elucidating whether leukemic stem cells exist, what their phenotype is, which mechanisms result in enhanced self-renewal and a disturbed differentiation profile, and whether we can restore the normal hematopoietic differentiation program by e.g. interfering at the genetic level or by utilizing novel therapeutical agents. We anticipate that our studies will lead to a more rational approach in the clinic of this highly malignant disorder.


LATEST NEWS!!

October 2018

paper by Bauke de Boer et al published in Cancer Cell, including issue highlight and Editorial

CancerCell de boer 2018
CancerCell de boer 2018

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August 2018

What is Leukemia? explained to the lay audience (in Dutch)

Leukemia explained to the lay audience
Leukemia explained to the lay audience

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August 2018

Media coverage on tv and radio (min 20-min 24) related to the Zwemelfstedentocht of Maarten van der Weijden

media coverage
media coverage

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July 2018

KWF project entitled Dissecting clonal heterogeneity in AML using the plasma membrane proteome was selected by Maarten van der Weijden as one of the 11 fundraising projects in his heroic effort to swim 200 km in the elfstedenzwemtocht! FANTASTIC!

see also:

https://www.11stedenzwemtocht.nl/onderzoek/

https://www.kwf.nl/onderzoek/welk-onderzoek-krijgt-geld/Pages/Elfstedenzwemtocht.aspx

zwemelfstedentocht
zwemelfstedentocht

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July 2018

Our time to organize the workshop for our ITN HaemMetabolome in Groningen. Great meeting, and great sailing afterwards at the Paterswoldse meer!

Sailing at the Paterswoldse meer
Sailing at the Paterswoldse meer

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July 2018

Susan Hilgendorf defends her thesis entitled The Long road: The autophagic network and TP53/ASXL1 aberrations in hematopoietic malignancies.

thesis Susan
thesis Susan

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December 2017

We performed transcriptome and ChIPseq experiments to compare direct and indirect targets of MLL-AF9. We conclude that BRD3/4 and the FLT3-TAK1/NF-kB pathways collectively control a set of targets that are critically important for the survival of human MLL-AF9 cells. Marco published his work in Plos ONE, which was a collaborative effort together with the Joost Martens lab in Nijmegen.

c
c

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October 2017

JJ co-organized EMBO workshop in Heidelberg on Humanized Mice in Biomedical Research.

EMBO workshop
EMBO workshop

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July 2017

Hendrik published his work on autophagy in leukemia, in Cell Death and Differentiation. The work indicates that targeting autophagy might provide new therapeutic options for treatment of AML

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July 2017

Further improvement of the humanized niche xenograft model! We genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34+ cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis. Work by Marco and Bauke, published in Experimental Hematology.

M
M

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March 2017

Smart niche usage: release its fat and burn it! JJ wrote an Inside Blood editorial on a paper by the Rushworth lab

Inside Blood commentary
Inside Blood commentary

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June 2017

KWF grant awarded to JJ Schuringa entitled: Using the plasma membrane proteome to dissect clonal heterogeneity and track disease progression in AML. Two PhD positions available!! See Vacancies

KWF grant awarded 2017
KWF grant awarded 2017

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June 2017

Oratie JJ: Dat zit hem in het bloed!

Oratie JJ party! (June 2017)
Oratie JJ party! (June 2017)

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October 2016

Antonella publishes her work on the development of improved humanized niche xenograft models. By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted, which covered all of the important genetic and risk subgroups. We found that by providing a humanized environment, stem cell self-renewal properties were better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift was observed as determined by exome sequencing. The human leukemia xenograft mouse models that we have established here will serve as an excellent resource for future studies aimed at exploring novel therapeutic approaches. The was a collaboration with Richard Groen, and was published in Blood. Also got the cover image and Inside Blood editorial.

cover
cover

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October 2016

Pallavi and Marco published their work on BCR-ABL and MLL-AF9-induced leukemia making use of humanized niche xenograft models in Leukemia.

Leukemia2016
Leukemia2016

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September 2016

Susan publishes her work on ASXL1 in Experimental Hematology. We conclude that ASXL1 is essential for erythroid development and differentiation and that the aberrant differentiation is, at least in part, facilitated via PRC2.

ExpHemat2016
ExpHemat2016

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September 2016

Thesis defense Pallavi Sontakke: Extrinsic and intrinsic cues involved in BCR-ABL induced leukemogenesis

Pallavi Sontakke defended her thesis (September 2016)
Pallavi Sontakke defended her thesis (September 2016)

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June 2016

Hendrik Folkerts published his nice work on autophagy in human CD34+ cells in Stem Cells

FolkertsStemCells2016
FolkertsStemCells2016
Lieke van der Helm defended her thesis (October 2016)
Lieke van der Helm defended her thesis (October 2016)

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April 2016

Pallavi published our work on metabolism in human leukemias in collaboration with the Ulrich Gunther lab in Birmingham in Plos One. From this collaboration we later on developed the ITN HaemMetabolome consortium.

SontakkePlosOne2016
SontakkePlosOne2016

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February 2016

We contributed to a European consensus document published in Haematologica

Haematologica
Haematologica

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January 2016

Vincent van den Boom and Henny Maat published their work on the non-canonical PRC1.1 complex in Cell Reports. see website

Graphical abstract Cell Reports
Graphical abstract Cell Reports
Marta's defense November 2015
Marta's defense November 2015

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October 2015

Matthieu Bosman defended his thesis in October 2015.

Thesis defense Matthieu Bosman
Thesis defense Matthieu Bosman

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September 2015


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May 2015

Capala et al
Capala et al

Marta Capala published a paper in Plos ONE showing that RAC2 fulfils an essential role in BCR-ABL transformed cells. Time-lapse confocal microscopy surprisingly revealed very distinct localisation of RAC1 and RAC2 in human hematopoietic stem/progenitor cells. Proteome studies to identify RAC1 and RAC2 interactomes revealed that RAC2 interacts with a set of mitochondrial proteins including mitochondrial transport proteins SAM50 and Metaxin 1. Downregulation of RAC2 or SAM50 impaired self-renewal associated with a decreased mitochondrial membrane potential and impaired mitochondrial integrity as determined by EM.


May 2015

HaemMetabolome
HaemMetabolome

HaemMetabolome awarded to JJ Schuringa. Within this Marie Skłodowska-Curie Actions Innovative Training Network (H2020-ITN-EJD, 2.4M euro) we aim to unravel metabolomic changes in haematological malignancies. Besides the UMCG/Experimental Hematology, the consortium consists of Ulrich Gunther (University of Birmingham, UK; NMR-based metabolomics/fluxomics), Marta Cascante (University of Barcelona, Spain; LC-MS/MS based metabolomics) en Harold Schwalbe/Hubert Serve (University of Frankfurt, Germany; leukemias).


October 2014

Capala et al
Capala et al

Marta Capala published a paper in Plos ONE showing that Engulfment and Motility protein 1 (ELMO1) is upregulated in AML CD34+ stem/progenitor cells which predicts poor prognosis in normal karyotype AML.


October 2014

KWF
KWF

Dutch Cancer Foundation (KWF) basic science grant awarded to JJ Schuringa, Edo Vellenga and Vincent van den Boom, entitled: Functional characterization of the non-canonical PRC1.1 complex as novel target in leukemia. € 567.200,-


September 2014

Bosman et al
Bosman et al

Matthieu Bosman published a paper in Blood in which he identified TAK1 as a critical kinase that regulates leukemic stem cell self-renewal.


September 2014

Schepers et al
Schepers et al

Hein Schepers published his paper in Leukemia showing that CITED2 is critically important for leukemic stem cells.


June 2014

Sontakke et al
Sontakke et al

Publication of book chapter on ex vivo expansion protocols of human leukemic stem cells


March 2014

Wierenga et al
Wierenga et al

Bart Jan Wierenga published his paper in Plos ONE in which he studied hypoxia-induced transcriptome changes in human stem/progenitor cells and identified that TGFb and hypoxia pathways converge on cell cycle regulation.


January 2013

vandenBoometal
vandenBoometal

Vincent van den Boom published his study in Blood in which he showed that PRC1 members fulfil non-essential roles in human stem/progenitor cells.


May 2013

Bonardi et al
Bonardi et al

Francesco Bonardi published his study in Molecular and Cellular Proteomics. By performing genome-wide transcriptome and proteome studies he identified leukemia-specific plasma membrane proteins that can be used for identification and targeting of leukemic stem cells.


April 2013

Horton et al
Horton et al

Sarah Horton published her paper in Leukemia showing that fetal stem/progenitor cells readily transform along the myeloid of lymphoid lineage, depending on extrinsic cues, while adult human stem/progenitor cells can only be transformed along the myeloid lineage, in line whith what is seen in patients.


April 2013

Valent et al
Valent et al

JJ Schuringa co-authored a paper in Nature Reviews Cancer on cancer stem cells.

Last modified:09 October 2018 4.16 p.m.