The group has a long tradition of cell adhesion research beginning from the co-discovery of fibronectin and identification of leukocyte surface proteins as adhesion proteins (integrins) and their ligands, the intercellular adhesion molecules (ICAMs). The group studies how the integrins are regulated, and specifically the role of integrin phosphorylation. In resting leukocytes the integrin α-chains are phosphorylated, but the β-chain not. The β2-chain is phosphorylated upon activation, but α-chain phosphorylation is a prerequisite for β-chain phosphorylation. The phosphorylations affect intracellular adapter protein associations and intracellular signaling, which we currently study in detail. The group also works on ICAMs and the role of integrins in malignant cells.
Many tumor types including leukemia and breast cancer are able to grow in the bone marrow and induce deep hypoxia. We study, how tumor cells absorb oxygen from surrounding normal tissue and in this way resemble embryonal cells. We have established a three-dimensional culture model of the bone marrow to develop specific inhibitors for tumor cell growth in hypoxia.
My projects involve studying the various pathways of inside-out activation and outside-in signaling involving the integrin LFA-1(αLβ2) and the effect of the constitutive cytoplasmic αL-chain phosphorylation in mediating these signal transduction mechanisms. LFA-1 can be activated through multiple cell surface receptors such as the T cell receptor or chemokine receptors and can mediate T cell rolling and transmigration through cross-talk with the integrin VLA-4 (α4β1). Exploring the different regulatory mechanisms of LFA-1 will shed light on how these pathways of inside-out and outside-in signaling are interconnected.