Group Leader:
Georges Lacaud
I graduated as a biotechnology engineer from the European Biotechnology School of Strasbourg (ESBS) in Strasbourg, France and subsequently worked in the biotech company Transgene SA in Strasbourg on gene therapy strategies against HIV. I obtained based on these studies my PhD from the University Louis Pasteur of Strasbourg, France and then did a postdoctoral fellowship at the National Jewish Medical Center in Denver, Colorado, USA studying early lymphoid cell development in Prof. Gordon Keller’s lab. I next moved to the Mount Sinai School of Medicine in New York, NY, USA where I worked on early hematopoietic development. In 2003, I joined the Paterson Institute for Cancer Research as a junior group leader and I currently head the Stem Cell Biology group.
Postdoctoral Fellows:
Christophe Lancrin
Flor Perez-Campo
Cristina Ferreras
Michael Lie-A-Ling
Scientific Officer:
Catherine Gavin / Ting Zheng
Graduate Students:
Patrycja Sroczynska
Olga Tsoulaki
Monika Antkiewicz
Stem Cell Biology Group
Applications are now open for our PhD programme starting in September 2010.The AML1/Runx1 transcription factor and its cofactor CBFβ, are frequent targets of gene rearrangements and mutations in human leukemias such as acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL). Consistent with its initial implication in leukemias, Runx1 has been shown to be critical for normal hematopoietic development. Runx1 deficient mice generate primitive nucleated erythrocytes, but lack all definitive erythroid and myeloid cells, indicating a complete block in definitive hematopoiesis. Using the in vitro differentiation system based on mouse embryonic stem (ES) cells, our goals are to further define the role of Runx1 in early hematopoietic development and how alterations of its function leads to leukemogenesis.
Early hematopoietic development
The earliest site of hematopoiesis in the mouse embryo is the yolk sac where blood islands, derived from mesodermal cells, develop at approximately day 7.5 of gestation. The yolk sac blood islands consist of two lineages, a population of primitive erythroid cells surrounded by a layer of angioblasts that eventually form the developing vasculature. more on early hematopietic development »
Evidence for the Hemangioblast
Although the blood islands were identified as the earliest site of hematopoietic and endothelial development almost 100 years ago, attempts to identify, isolate and characterize the precursors representing these initial stages of lineage development, including the elusive hemangioblast, have been largely hampered by the inaccessibility of the early mammalian embryo. The differentiation of embryonic stem (ES) cells in culture offers a powerful alternative approach to study the development of such lineages that are established very early in embryonic life. more evidence for the hemangioblast »
Molecular regulation of early hematopoiesis
Insights into the molecular regulation of early hematopoiesis have come from targeting studies that identified specific genes as key regulators in this process. One such gene, AML1 (Runx1 or CBFβ2) was originally identified in translocations associated with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL). Translocations of AML1 and its cofactor CBFβ account for more than 30% of AML and 25-30% of ALL. more on molecular regulation »
A critical function of Runx1 in Hemangioblast development
To investigate the role of Runx1 at the earliest stage of hematopoietic commitment, we have analyzed its expression pattern and function during ES/EB differentiation and in early yolk sac development. Expression analyses indicated that Runx1 is expressed in yolk sac mesodermal cells prior to the establishment of the blood islands and within the BL-CFC in EBs. more on Runx1 »
Downstream targets of Runx1
Runx1 has been shown to participate in the regulation of expression of a number of different genes including IL-3, myeloperoxidase, neutrophil elastase, M-CSF, GM-CSF and T cell receptors that are involved in relatively late stages of hematopoietic development. more on downstream targets of Runx1 »
An early role of Runx1 in mesoderm development
Our studies have also indicated that although Runx1+/- EBs generate normal number of blast colonies, the kinetics of development of the BL-CFC precursors is accelerated relative to the pattern observed in wild type EBs. Gene expression analyses have indicated that the acceleration is already initiated at the level of mesoderm commitment. more about the early role of Runx1 in mesoderm development »