Home > Faculty > Primary > Jensen

Department of Pharmacology
Liselotte E. Jensen, Ph.D.

Education:

1994	M.Sc. (Chemistry and Biotechnology)	University of Aarhus, Denmark
1997	Ph.D. (Biotechnology)	University of Aarhus, Denmark

Research Summary:
The interleukin-1 (IL-1) system comprises a complex network of extracellular cytokines, transmembrane receptors and intracellular signaling molecules. Together these proteins play an essential role in orchestrating the initiation of immune responses by regulating gene expression. While these mechanisms are fundamental for preventing and eliminating infections, they may also contribute to pathologies such as allergy, atherosclerosis, hepatitis, inflammatory bowel disease and psoriasis. Furthermore, many chronic inflammatory conditions, e.g. hepatitis and inflammatory bowel disease, are associated with an increased risk of cancer.

The laboratory examines how signaling by IL-1 is regulated and how dysfunction of the involved mechanisms leads to disease. Current focus is on two groups of proteins: the interleukin-1 receptor accessory proteins (IL-1RAcP) and the Pellino proteins.

Two alternative splice variants are expressed from the IL-1RAcP gene. One isoform is a membrane bound receptor co-factor, which is involved in signal transduction and initiation of inflammation. The second isoform is a shorter soluble and secreted protein with anti-inflammatory activity. We recently discovered a novel third alternatively spliced soluble IL-1RAcP isoform and determined that cellular stress induce changes in the proportions of the inflammatory membrane bound IL-1RAcP and the anti-inflammatory soluble IL-1RAcP isoforms. These changes may represent a mechanism whereby stressed cells become less responsive to inflammatory stimuli, thereby preventing tissue damage.

The Pellino proteins, Pellino1 and Pellino2, have recently been shown to be involved in signal transduction. We have identified a third Pellino protein, Pellino3, and shown that it interacts with several IL-1 signal transduction proteins. Our preliminary data suggest that the Pellino proteins may act as scaffolds directing up-stream signaling molecules to different down-steam signaling sub-pathways, such as mRNA stabilization and activation of the transcription factors AP-1 and NF-κB.

We utilize tissue culture and animal models to examine biological activities of the studied proteins, and aim to correlate observations from our model systems with data obtained from normal and pathological specimens. Our ultimate goals are to identify defective signaling pathways in diseases, and utilize this knowledge to develop novel therapeutic strategies.