Ploug Group – University of Copenhagen

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Ploug Group

Our research is focused on structural and functional aspects of proteins involved in cellular invasion and matrix degradation. 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 clinical setting, particularly within the field of oncology.

At present our primary focus is on the urokinase-type plasminogen activator receptor (uPAR) and on the related membrane proteins C4.4A, Haldisin and GPIHBP-1. The structure-function relationships in these proteins are decoded using a variety of purified recombinant proteins, monoclonal antibodies, surface plasmon resonance (SPR), and on a collaborative basis by biophysical technologies such as X-ray crystallography, SAXS and HDX-MS.

Our core expertise is on kinetic assessment of protein-ligand interactions by SPR. The biochemical properties that we uncover in purified systems are subsequently tested for their functional importance in various cellular settings using cell lines expressing the protein variants in question and by epitope-mapped monoclonal antibodies.

In collaborative efforts we attempt to transfer our findings into clinical settings, as exemplified by our recent successful studies with non-invasive imaging of uPAR expressing tumors by positron emission tomography.

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Key results

  • uPAR is a GPI-anchored protein and is deficient in leukocytes from PNH patients
  • Crystal structures solved for human and murine uPAR
  • Delineating functional and structural binding-sites on uPAR for uPA and vitronectin
  • Clarifying the structural basis for the allosteric regulation of ligand binding in uPAR
  • Development and characterization of small, high-affinity peptide antagonists of uPA•uPAR binding
  • Pre-clinical applications of one of our uPAR-targeting peptides in mouse models for non-invasive PET-imaging and localized radiotherapy
  • Defining C4.4A expression levels  as a strong biomarker for poor prognosis in patients with non-small cell lung adenocarcinomas
  • Generating and characterizing a C4.4A-deficient mouse