Benedikte Jacobsen

Ph.d.

Key Research Interests
Clinical and functional relevance of the protein C4.4A in non-small cell lung cancer

Current Project
My research is focused on the Ly6/uPAR/alpha-neurotoxin protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor (uPAR). I have recently characterized the immunohistochemical expression pattern of C4.4A in two histological subtypes of non-small cell lung cancer, adenocarcinomas (AC) and squamous cell carcinomas.
These studies have revealed that C4.4A is expressed at very early stages in the progression to these malignant pulmonary carcinomas. It is absent from normal bronchial tissue, but appears in the reactive changes of hyperplasia and metaplasia, indicating that C4.4A is a marker of very early squamous differentiation. In the alveolar compartment, the normal epithelium is also devoid of C4.4A, which, however, is present in a fraction of the AC precursor lesion, atypical adenomatous hyperplasia. With a view to our earlier studies revealing a correlation of high levels of C4.4A and poor survival of AC patients, this suggests that C4.4A could be an early biomarker for a more malignant subtype of AC.

In collaboration with Dr. Thomas Muley (Thoraxklinik, Heidelberg, Germany), I have furthermore validated our previous observations on the prognostic impact of C4.4A in an immunohistochemical, retrospective study of an independent and larger patient cohort. Statistical analysis of survival confirmed that C4.4A is a significant prognostic factor in AC patients.

Together, these data support that C4.4A is a potentially interesting prognostic biomarker in pulmonary AC, the clinical value of which will be explored in future projects. Very recent data from esophageal cancer cell lines have revealed that the gene encoding C4.4A, LYPD3, is negatively regulated by the tumor suppressor LKB1. A similar correlation in lung cancer, where LKB1 inactivating mutations are indeed found in a fraction of ACs, would provide an explanation for the ectopic expression of C4.4A seen in pulmonary AC. The putative link between C4.4A positivity and LKB1 deficiency will therefore be the focus of new investigations on C4.4A.

Career
2011: PhD from the University of Copenhagen (Faculty of Health Sciences), Copenhagen, Denmark
Project performed at the Finsen Laboratory, Rigshospitalet
Project title: Expression and prognostic significance of C4.4A in non-small cell lung cancer

2010: 8 months stay at the Laboratory for Experimental Organogenesis (LOEX), Québec, Canada

2007: Research assistant, Finsen Laboratory, Rigshospitalet

2007: M.Sc. Engineering (Biotechnology) from the Technical University of Denmark (DTU)
Master project performed at the Finsen Laboratory, Rigshospitalet
Project title: Purification and photoaffinity labeling of uPAR with synthetic peptide antagonists
Bachelor project performed at Pharmexa A/S, Hørsholm
Project title: Capillary electrophoresis of glycoproteins. Analysis of glycoforms of human epidermal growth factor receptor 2

2003-2004: Exchange program at Universidad Autónoma de Madrid, Spain

2000: University of Oslo, Norway
Physics, chemistry, Examen Philosophicum

1998: International Baccalaureate from Nesbru videregående skole, Norway