Project A1: Checkpoint control in hematopoietic stem cells - contribution to genetic and epigenetic instability in leukemia

Principal Investigators

Prof. Dr. Hartmut Geiger / Dr. Maria Carolina Florian
Institute of Molecular Medicine
University of Ulm
Life Sciences Building N27 and N24
James-Franck-Ring
89081 Ulm
Phone: 0731-50-26700 / 0731-50-26714
hartmut.geiger(at)uni-ulm.de / carolina.florian(at)uni-ulm.de

Curriculum Vitae Hartmut Geiger
Curriculum Vitae Maria Carolina Florian

Summary

Stem cells are frequently the underlying cancer-initiating cells, especially in leu-kemia. Leukemia is strongly associated with DNA mutations as well as changes in the epigenetic landscape of stem cells, implying a role for genetic and epigenetic instability in leukemia initiation and progression. Our novel preliminary data demonstrate that hematopoietic stem cells (HSC) do actively engage a mitotic check-point as well as a G2 checkpoint. Our novel hypothesis to test is that failure of activation of the mitotic check-point or other late cell cycle checkpoints (like the G2/M) will result in DNA mutations and/or alterations in the epigenetic architecture of stem cells upon subsequent division and by this means contribute to leukemia initi-ation and progression. Specific objectives are: (1) Define mechanisms of activation of the mitotic checkpoint in HSCs; (2) Determine consequences of a faulty checkpoint activation; and (3) Determine the role of Ube2g1 and cohesin in cell cycle checkpoint activation upon DNA damage.

For a list of project-related publications, please go to this page