Research Overview

The Laboratory for Immunological and Molecular Cancer Research (LIMCR), headed by Univ. Prof Dr. Richard Greil, has put its emphasis on basic and translational research in leukemic and lymphocytic diseases. Our research activity is particularly focussed on B-cell chronic lymphocytic leukaemia and multiple myeloma, both representatives of B-cell malignancies. Over many years intense investigations of these tumour entities have broadened our understanding of mechanisms and effectiveness of cytotoxic therapies. We now know the modalities and signals that lead to cell death caused by cytotoxic agents and factors that suppress or even inhibit the effects of the latter. Understanding the mechanisms of resistance enables us to develop new and improved therapies.

Whether a certain anti-tumour therapy is effective in vivo is not only defined by the molecular repertoire of the tumour cells. We have already shown that the micro-environment in bone marrow, lymph node and blood vessels also contribute crucially to the success of the therapy. This is why we are particularly interested in the interactions of tumour cells and „normal” cells in the micro-environment. If we can manage to inhibit tumour-supportive signals provided by the micro-environment, improved therapies with respect to sensitivity, resistance and side-effects will be available (Group 4: Tumorimmunology und Chemoimmuntherapy, Dr. Roland Geisberger).

Using suitable mouse models (Group 2: Murine Lymphoma Models, PD Dr. Alexander Egle) we investigate the emergence of these malignancies in order to identify factors that initiate tumorigenesis and determine a moderate or aggressive course of disease. This mouse model (TCL-1) is also suitable to investigate the role of PKB/AKT during development of CLL cells.

We compare cellular gene expression of stable and progressive tumours by a high throughput method (Group 3: Apoptosis regulation and genomic profiling, Dr. Olaf Merkel). This provides us with a complete genetic and proteomic profile of tumour cells. Additionally, this method can be helpful to identify new effective substances for tumour therapy.

Spacial and thematical proximity to the clinic allows us to investigate the influence of any new differerential factors on diagnosis and prognosis in an extended sample collective (group of Mag. Gabriele Brachtl). Confirmation of our results from the clinic should lead to the development of new, specific molecular therapies that enable us to influence these factors.

The role of integrins and chemokines in the migration of CLL cells and the putative leukaemia-initiating cells through blood vessels, their settlement in bone marrow, spleen or lymph nodes and their interaction with the so-called microenvironment is studied by Group 1: Leukemia / Cancer Stem Cells, Dr. Tanja N. Hartmann. The elucidation of these biological processes will build the basis for development of novel strategies aiming at the prevention of tumour expansion und the development of more active anti-tumour treatment. Following identification of the putative leukaemia-initiating cells we will be able to address the unresolved question whether these cells evade the established standard therapies and whether we have to focus on the development of novel targeting strategies.

The research teams of the LIMCR work in close cooperation with the III. Medical Department of Hematology, Oncology, Hemostaseology, Rheumatology and Infectiology (also hreaded by Univ. Prof. Dr. Richard Greil), the hematological routine laboratory (Dr. Victoria Faber), the faculty of natural sciences at Paris-Lodron University Salzburg and the Paracelsus Medical Private University Salzburg.