Peter Carmeliet - University of Leuven (Sub-project 1)
Center for Transgene Technology and Gene Therapy
Flanders Interuniversity Institute of Biotechnology
University of Leuven
Campus Gasthuisberg O & N (9th floor)
Herestraat 49
3000 Leuven, Belgium
Phone: +32 16 345783
Fax: +32 16 345990
e-Mail: peter.carmeliet@med.kuleuven.be
Website: http://www.kuleuven.be/mcm/
In this project, we will investigate the molecular mechanisms underlying precursor cell retention and mobilization, with the hope to identify novel therapeutic strategies to promote tissue regeneration. Preliminary results indicate critical roles of membrane-bound uPAR and prominin-1 in BM precursor cell retention, and of soluble uPAR and plasmin in BM precursor cell mobilization. These preliminary data will be further confirmed via loss-of-function versus gain-of-function studies in mice using various genetic and pharmacological approaches. We will study the role of membrane-bound and soluble uPAR in BM precursor cell retention and mobilization by using mice lacking uPAR and by administering recombinant soluble uPAR fragments. Phenotyping will include various models of retention (e.g. homing, engraftment) and mobilization (e.g. G-CSF, chemotherapy, ischemia), and state-of-the-art precursor cell analysis. We will further investigate the role of prominin-1 in BM precursor cell retention and mobilization by using mice lacking prominin-1 (available) and phenotyping as mentioned above.