Benedikte Jacobsen

Ph.d. student

Key Research Interests
C4.4A; Non-small cell lung cancer; Immunohistochemistry; Double immunofluorescence

Current Project
In my PhD project (running 2008-2010), I work with the novel protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor (uPAR), which has been implicated in cancer invasion and metastasis. The specific biological function of C4.4A remains elusive, however, and the aim of my project is therefore to delineate some of the biochemical mechanisms linking C4.4A to cancer, through structural and functional investigations along with expressional studies in human cancer. Such knowledge on the molecular basis for malignant tumor progression would enable the development of targeted cancer therapies and improvements in prognosis.

We have recently established that high tumor expression of C4.4A in patients with non-small cell lung cancer (NSCLC) is correlated with survival, where patients with adenocarcinomas suffered a particularly severe disease progression. I will further substantiate this finding by examining an independent NSCLC patient material for the prognostic significance of C4.4A. In conjunction with this, a descriptive study on the expression of C4.4A in premalignant lesions of NSCLC will be performed by immunohistochemistry and double immunofluorescence. The reported association of C4.4A with laminin-1, laminin-5 and galectin-3 is indicative of a putative role of the protein in cell adhesion and migration. Further investigations into the interactions with these ligands will be conducted, while also searching for new potential ligands of C4.4A. In addition, we will, in a collaborative effort, try to solve the three-dimensional structure of C4.4A by X-ray crystallography, to investigate whether this protein has a similar hydrophobic ligand-binding cavity as we found for uPAR, which would be a potential target for small molecule anti-cancer drugs.

Career
2007 Master of Science from The Technical University of Denmark (DTU)