Michael Ploug

Ph.d., DSc.

Group Leader - Curriculum vitae

Key Ressearch Interests
Research in my group is predominantly focused on structural and functional aspects of proteins involved in cellular invasion and matrix degradation. The cellular receptor for the urokinase-type plasminogen activator (uPAR) and its structural homologues C4.4A and Haldisin are presently being the primary components under study. The ultimate goal of these studies is to elucidate the function of these proteins in vitro and in vivo and to facilitate the translation of these findings into a clinic setting, particularly within the field of oncology.

Current projects
See Ploug Group - Current projects

Major research achievements
Reported for the first time that the polypeptide chains in inter-α-tryisin inhibitor are covalently linked by carbohydrate (3). In 1991, we demonstrated that the urokinase-type plasminogen receptor (uPAR) is linked to the cell surface via a glycosyl-phosphatidylinositol membrane anchor (7) and as a consequence uPAR expression is deficient in leukocytes from patients with the bone marrow defect paroxysmal nocturnal hemoglobinuria (11). We also defined uPAR as the first protein having multiple Ly6/uPAR/α-neurotoxin domains (8,19, 22). Importantly, we solved the first crystal structures of both human and mouse uPAR in collaboration with Dr. Menéz (CEA, Saclay, France) and Dr. Huang (BIDMC, Harvard, Boston, US), respectively (44, 64). Through an exhaustive mutagenesis analysis, we have defined the functional epitopes for the interaction between uPAR and uPA (31, 48), vitronectin (51) and a large panel of monoclonal antibodies (71). This has enabled us to alter the function of uPAR through rational design (64). In a collaboration with Dr. Bugge (NIH, Bethesda, Maryland, US), we have used this information to generate of a new transgenic mouse strain where the impact of the uPA•uPAR interaction sensu stricto can be scrutinized in normal physiology as well as under defined pathological conditions (65).
Finally, in an international collaboration with Dr Chen, Stanford, CA, US we demonstrated the first non-invasive imaging of uPAR in live mice by positron emission tomography(57). We developed this high-affinity targeting probe several years before by combinatorial chemistry (34) and among other things we used this peptide antagonist to solve the first crystal structure of uPAR published (44). We are presently pursuing translational aspects of this uPAR targeting probe in collaboration with Dr Andreas Kjær (Cluster for Molecular Imaging, Copenhagen University).

The numbers in brackets refer to the corresponding references in my publication list.