header-image

Prof Gerald (G) de Haan PhD

Training

1990

University of Groningen, Groningen, the Netherlands   M.Sc. (Medical Biology)

1995

University of Groningen/University of Cologne   Ph.D. (Hematology)

1995-1998

Post-doctoral fellow in the lab of Prof.Dr. Gary Van Zant, Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Kentucky, Lexington, KY, USA

Thesis

Regulation of hemopoietic cell production. In vivo manipulation by hemopoietic growth factors and cytotoxic drugs. University of Groningen, 1995.

Research interests

Gerald de Haan has focused his entire scientific career on the identification of molecular mechanisms that control selfrenewal of hematopoietic stem cells. His early scientific contributions include papers in which the aging hematopoietic stem cell phenotype was described for the first time. He was the first to use the power of complex mouse genetics to identify genetic loci that regulate lifespan in mice and discover that these same loci were also controlling stem cell turnover rates. His lab was the first to use expression quantitative traits to search for loci that regulate stem cell-specific transcriptomes. His lab was also one of the first to clonally study the behavior of single young and aged stem cells. His lab has used multiple genome-wide approaches to search for HSCs regulatory genes. This resulted in the identification of the Polycomb group proteins Ezh2 and microRNA125a, and led to functional studies in which these genes were shown to crucially regulate HSC selfrenewal and their leukemic derailment. The identification of the polycomb group gene Ezh2 spurred further efforts in establishing the role of the epigenetic machinery for HSC functioning, and identified Cbx7 as a key stem cell gene. These studies showed the importance of epigenetic modifications in hematopoietic stem cell selfrenewal. Only recently it has become apparent that a significant number of mutations in (elderly) patients with myelodysplastic syndromes and leukemia occur in epigenetic genes, and appear to confer a proliferative advantage to stem cells. His lab also developed technology to assess the fate of single (young and aged) HSCs, using either single cell transplants, or barcoding single HSCs and reading out clonalbehavior using next generation sequencing approaches. His most recent studies have identified multiple novel HSC cell surface receptors that are specifically or preferentially expressed by aged HSCs, and current efforts in his lab aimto resolve the biological relevance of these novel HSC aging genes.

Technology

HSC purification, HSC culturing, HSC transplantations, genetic modifications, genome-wide epigenetic and gene expression analyses

Resume

2021-present:

Director of Research, Member Executive Committee, Sanquin Blood Supply Foundation. Amsterdam.

2016-2021:

Scientific Director ERIBA (European Institute for the Biology of Aging) and Head of Department of Biology of Ageing

2014-2017:

Dean Learning Community Molecular Medicine, Bachelor Program of Medical School University of Groningen.

2009-2016:

Scientific co-Director ERIBA (European Institute for the Biology of Aging)

2005-present:

Professor of Molecular Stem Cell Biology, University Medical Center Groningen.

Aug. 2005:

Sabbatical leave to Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA.

July 2002:

Sabbatical leave to Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA.

2003-2005:

Associate Professor, Dept. of Stem Cell Biology, University of Groningen.

July 2000:

Sabbatical leave in lab of Dr. Ihor Lemischka, Dept. Mol.Biol., Princeton University, Princeton, NJ., USA

1998-2003:

Research Scientist, Experimental Hematology, Groningen institute for Drug Studies, Groningen, the Netherlands.

 

Key papers

1. De Haan G, Gelman R, Watson A, Yunis E, Van Zant G (1998). A putative gene causes variability in lifespan among genotypically identical mice. Nature Genetics 19:114-16.
2. De Haan G, Weersing E, Dontje B, van Os R, Bystrykh LV, Vellenga E, Miller G. (2003). In vitro generation of long-term repopulating hematopoietic stem cells by FGF-1. Developmental Cell 4: 241-51.
3. Bystrykh LV, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang J, Manly KF, Lu L, Chesler E, Alberts R, Jansen RC, Williams RW, Cooke M, de Haan G. (2005) Uncovering regulatory pathways that affect hematopoietic stem cell function using ‘genetical genomics’. Nature Genetics 37:225-32.
4. Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G (2006). The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood, 107(5):2170-9
5. Brad Dykstra, Sandra Olthof, Jaring Schreuder, Martha Ritsema, and Gerald de Haan (2011). Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med. 19;208(13):2691-703
6. Karin Klauke, Visnja Radulovic, Mathilde J.C. Broekhuis, Ellen Weersing, Erik Zwart, Sandra Olthof, Martha Ritsema, Sophia Bruggeman, Xudong Wu*, Kristian Helin*, Leonid Bystrykh, and Gerald de Haan (2013).  Polycomb Cbx orthologs mediate the balance between Hematopoietic Stem Cell self-renewal and differentiation. Nat Cell Biol. 15(4):353-62
7. Verovskaya E, Broekhuis MJ, Zwart E, Ritsema M, van Os R, de Haan G, Bystrykh LV (2013). Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood 122 (4): 523-32.
8. Edyta E. Wojtowicz, Eric R. Lechman, Karin G. Hermans, Erwin M. Schoof, Erno Wienholds, Ruth Isserlin, Peter A. van Veelen, Mathilde J.C. Broekhuis, George. M.C. Janssen, Aaron Trotman-Grant, Stephanie M. Dobson2, Gabriella Krivdova, Jantje Elzinga, James Kennedy, Olga Gan, Ankit Sinha, Vladimir Ignatchenko, Thomas Kislinger, Ellen Weersing, Mir Farshid Alemdehy, Hans W.J. de Looper, Bader, GD, Martha Ritsema, Stefan J. Erkeland, Leonid V. Bystrykh, John E. Dick and Gerald de Haan (2016). Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors. Cell Stem Cell.19(3):383-96. doi: 10.1016/j.stem.2016.06.008.
9. Jung J, Buisman SC, Weersing E , Dethmers-Ausema B1, Zwart E, Schepers H, Dekker MR, Lazare SS, Hammerl F, Skokova J, Kooistra SM, Klauke K, Poot RA, Bystrykh LV and de Haan G (2019). CBX7 induces self-renewal of human normal and malignant hematopoietic stem and progenitor cells by canonical and non-canonical interactions. Cell Rep. 12;26(7):1906-18.
10. Svendsen AF, Yang D, Kim KM, Lazare S, Skinder N, Zwart E, Mura-Meszaros A, Ausema A, von Eyss B, de Haan G*, Bystrykh LV* (2021). A comprehensive transcriptome signature of murine hematopoietic stem cell aging. Blood. 2021 Apr 19;blood.2020009729. doi: 10.1182/blood.2020009729.

Other activities

2020-present

Member Scientific Advisory Board of Centre for Genome Organisation and Maintenance (CenGEM) at Brunel University London.

2019-present

Member ZonMW Rubicon Programma.

2019-present

Member NWO ENW-Klein 4 grant evaluation committee

2017-2024

Member ZonMW Programma Translationeel Onderzoek

2010-present

Founding member and Treasurer of Dutch Society for Stem Cell Research (DSSCR)

2014-2018

Member Medical Research Council UK (MRC-UK) Molecular and Cellular Medicine Board

2011-2012

President International Society for Experimental Hematology.

2010-2016

Member Scientific Research Council (Wetenschappelijke Raad) Dutch Cancer Society/KWF

2009-2014

Scientific Advisory Board Landsteiner Stichting voor Bloedtransfusie Research (LSBR, Dutch Blood Bank Research Foundation )