Dominique Bonnet

Haematopoietic Stem Cell Laboratory 

The haematopoietic (blood) system produces billions of mature blood cells every day. In order to maintain the homeostasis of the system, a tight regulation is thus in place. Our lab is interested in understanding the regulation of the haematopoietic stem cells (which produce all the mature cells for the entire life of an individual), both in normal development and during leukaemia. We are specifically interested in the extrinsic mechanisms that regulate these cells and how we could intervene in order to eradicate the leukaemic stem cell.

The laboratory is interested in studying both normal human haematopoietic stem cells (HSCs) and leukaemic stem cells (LSCs). As an assay for the activity of these cells, we perform xenotransplantation into a NOD/SCID (non-obese diabetic/severe combined immunodeficient) mouse model. Comparison of the resulting engraftment phenotype, and investigation of the molecular pathways regulating cellular functions, especially self-renewal, are the focus of the group.

We are also investigating the relationship between normal HSC, LSC and their microenvironment. For that we have developed in vivo imaging techniques allowing us to visualise and define the normal and leukaemic stem cell niche. We have developed a 3D scaffold system where human stroma cells could be co-cultured in vivo with HSC or LSC to study the effect of the interaction and study the cross-talk between stroma and HSC/LSC. All these projects should shed light into pathways or interactions that are more specifically used by LSC cells and, thus, where therapeutic intervention might be developed.

Figure 1A and 1B

Figure 1A (left) and 1B (right)

Figure 1: (A) Transversal section of a tibia showing in purple the bone and in red vessels. This shows the complex and dense vascularisation in long bone even in the zone close to the bone (endosteal region) thought to be devoid of vessels. (B) 3D tracking of human leukaemia (HL60 cell line) in live bone marrow.

Selected publications

Pizzitola I et al.  Chimeric Antigen Receptors against CD33/CD123 antigens specific target primary Acute Myeloid Leukemia cells in vivoLeukemia, 2014,28(8):1596-605.

Anjos-Afonso F, et alCD34(-) cells at the apex of the human hematopoietic stem cell hierarchy have distinctive cellular and molecular signaturesCell Stem Cell; 2013; 13(2):161-174.

Rouault-Pierre K, Onieva Lopez L, et alHIF-2α protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stressCell Stem Cell; 2013:13 (5): 549-63

Yeung J, et al.  β-catenin mediates the establishment and drug resistance of MLL leukemic stem cellsCancer Cell; 2010; 18:606-618

Taussig D, et alLeukemia-initiating cells from many acute myeloid leukemia patients with mutated nucleophosmin reside exclusively in the CD34- fractionBlood; 2010; 115(10):1976-84.

Taussig DC, et al., Bonnet D. Anti-CD38 antibody mediated clearance of human repopulating cells masks the heterogeneity of leukemia initiating cellsBlood; 2008; 112:568-75.

 

Dominique Bonnet

Dominique Bonnet

dominique.bonnet@crick.ac.uk
+44 (0)20 379 61198

  • Qualifications and history
  • 1993 PhD, University of Paris VII, France
  • 1993-1997 Postdoctoral Research Fellow, Hospital for Sick Children, Canada
  • 1998 Assistant Professor, Coriell Institute for Medical Research, USA
  • 2001 Adjunct Assistant Professor, University of Pennsylvania, USA
  • 2001 Established lab at the Imperial Cancer Research Fund, UK (in 2002 the Imperial Cancer Research Fund became Cancer Research UK)
  • 2015 Group Leader, the Francis Crick Institute, London, UK