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Department of Internal Medicine


  • Biomarker- based therapeutic prevention

    Biomarker- based therapeutic prevention of bone metastases in breast cancer: Defining the pathophysiologic impact of the endosteal niche

    • Project Number: LSC18_010
    • Project Lead: Sonia Vallet, Karl Landsteiner University of Health Sciences / Division of Internal Medicine 2 (University Hospital Krems)
    • Project Partner: IMC University of Applied Sciences Krems / Department of Life Sciences
    • Duration: 36 months starting from 01.12.2019


    Despite unprecedented advances in breast cancer (BC) treatment strategies during the last decade, up to one third of patients relapse of which 70% develop bone metastases. Manipulating the bone microenvironment, the osteoblast
    (OB)- rich endosteal niche in particular, at early BC stages may prevent disease relapse, reduce the rate of bone metastases and thereby ultimately decrease patient mortality. However, biomarkers in BC patients at high-risk to develop bone metastases are currently unknown. In addition, effective strategies to prevent bone metastases are lacking. Here, we propose to unravel the pathophysiologic role of the endosteal niche, OB lineage cells in particular, during
    early phases of bone metastasis in BC. Innovative in vitro models of OB differentiation will be generated, in order to ultimately identify: (1) reliable biomarkers that predict the risk of bone metastatic disease; and (2) novel bone modifying
    agents (BMAs), that prevent early bone metastatic events in BC. Based on results of this application biomarkerdirected clinical studies with BMAs will be initiated. Aim 1: A novel dynamic 3D model of the OB-rich endosteal bone metastatic niche in BC will be generated by using poly-{epsilon}- caprolacton scaffolds loaded with mesenchymal cells in a RCCS™ bioreactor. OB differentiation will be assessed by morphological and functional analyses. In addition, OB-lineage cells will be characterized by gene expression and secretion of soluble markers. The impact of tumor cells on the structure and composition of the bone niche will be studied by adding BC cells of different metastatic potential. Aim 2: Since the endosteal surface is the preferred seeding and thriving area for tumor cells in the bone, the supportive role of OB-lineage cells on BC cell migration, adhesion, proliferation and drug resistance will subsequently be studied by using functional assays, imaging studies and histological examinations. Screenings for soluble markers representative for OB- mediated effects on tumor cells will additionally be performed. Aim 3: Understanding molecular mechanisms behind the early metastatic colonization of the bone is a pivotal step towards the development of preventive treatment strategies for BC patients at high risk of skeletal involvement. Conventional and investigative BMAs will therefore be tested for their ability to prevent bone metastases and to overcome OB- mediated BC cell migration, proliferation and drug resistance.


    • Project Lead: Martin Ursli, Karl Landsteiner University of Health Sciences / Division of Internal Medicine 1 (University Hospital St. Pölten)
    • Duration: 24 months starting from 01.10.2019
  • MFSD1 Transporter

    Investigationg the role of the novel major superfamily facilitator transporter

    • Project Number: LSC16_021
    • Project Lead: Daria Siekhaus, IST Austria
    • Project Partner: Karl Landsteiner University of Health Sciences / Division of Internal Medicine 1 (University Hospital St. Pölten)
    • Duration: 36 months starting from 01.08.2017


    Metastatic spread causes 90% of all tumor related fatalities and thus represents the greatest challenge for cancer patient survival. Tumor cells need to become motile and cross vascular barriers for metastatic spread. How these processes are controlled is not yet fully understood. The laboratory of Dr. Daria Siekhaus has identified a novel transporter, CG8602, required for Drosophila macrophages to invasively migrate into the tissues of the embryonic germband. Data from the Siekhaus lab point towards a role for CG8602 in regulating the glycosylation and stability of proteins that limit tissue entry. CG8602 appears necessary for the increased level of T antigen present on the surface of macrophages invading the tissue of the germband. Intriguingly, increased levels of T antigen have been found in metastatic cancer and antibodies against T antigen can reduce metastasis. This raised our interest in translating our findings into vertebrates, and Dr. Siekhaus recruited a post-doctoral fellow, Dr. Marko Roblek, with extensive experience in studying metastasis in mice back to Austria from Switzerland. This fellowship will help pay for his salary and material costs and thus enable him to conduct the work that will form the foundation for establishing his own independent lab. The mammalian ortholog of the CG8602 transporter, called MFSD1, is highly conserved, and belongs to the solute carrier superfamily (SLC). Yet its functions remain unknown due to a lack of prior studies. We seek to examine the role of MFSD1 in tumor cells during mouse metastatic initiation, We also will examine whether and how MFSD1 is involved in regulating protein glycosylation, protein stability, and how these potential changes affect the regulation of invasive tumor migration. By analyzing the function of MFSD1 and its interaction partners we aim to uncover the mechanism from aberrant glycosylation to the invasive migration phenotype observed during metastatic spread of tumors. This will include analysis of cell surface proteins, signaling cascades, and transcriptional regulation of cell migration. To test the relevance of these findings for the clinic, we are partnering with Dr. Wiesholzer and Dr. Kitzwoegerer at the Clinical Division for Internal Medicine, KLU University St Poelten. By analyzing resected tumor tissue from patients we will determine whether the level or localization of MFSD1 can be correlated with disease prognosis. We are eager to transfer findings from Drosophila to the vertebrate system in the context of metastasis research. Our prior data leads us to believe that this will lead to the description of an evolutionarily conserved mechanism that regulates invasive migration regulation from fly to vertebrates. This work can lay the ground work for
    understanding the basic biology of a novel vertebrate gene involved in regulating invasion and metastasis, and thus for the eventual development of a new therapeutic target and diagnostic biomarker for the clinic.

  • Tumor Cachexia

    Metabolic characterization of chronic inflammatory conditions such as metabolic syndrome and tumor cachexia

    • Project Number: LSC14_021
    • Project Lead: Martin Pecherstorfer, Karl Landsteiner University of Health Sciences / Division of Internal Medicine 2 (University Hospital St. Pölten)
    • Project Partner: IMC University of Applied Sciences Krems / Applied Bioanalytics & Drug Development, University of Vienna / Department of Analytical Chemistry, Medical University Graz / Core Facility Mass Spectrometry, Medical University of Vienna / Institute of Medical Statistics, Rudolfstiftung Hospital / Karl Landsteiner Institute for Obesity and Metabolic Diseases
    • Duration: 42 months starting from 01.02.2016


    The clinical picture of the metabolic syndrome (MeS) is characterized by obesity, hypertension, insulin resistance and pathological blood lipid levels. Furthermore, the existence of a chronic inflammatory state in the adipose tissue leads to changes in the lipid metabolism of the fat cells. As a result, this leads to a disturbed uptake, deposition and release of lipids and free fatty acids. Interestingly, in the blood plasma of patients with tumor cachexia (CaC), lipid and inflammatory markers are similar to those of the metabolic syndrome. Tumor cachexia (CaC) is the term for a metabolic disorder that occurs as a result of cancer. This disorder leads to cachexia of the patient and emaciation.
    For research, this raises two important questions: What are the pathophysiological processes in the metabolic syndrome and the tumor syndrome cachexia? Is there a common biological marker for the pathophysiological processes in metabolic syndrome and tumor cachexia?


  1. 14 Mar

    Open House at KL University - March 2020

    14. March 2020, 10:00 - 14:00
    Karl Landsteiner University, Dr.-Karl-Dorrek-Straße 30,3500 Krems, Trakt Y, Erdgeschoß
  2. 27 Mar

    International Skills Lab Symposium 2020

    27. March 2020, 09:00 - 28. March 2020, 18:00
    Karl Landsteiner Privatuniversität für Gesundheitswissenschaften, Skills Lab, Trakt Y
  3. 16 Nov

    Open House at KL University - November 2019

    16. November 2019, 10:00 - 14:00
    Karl Landsteiner Privatuniversität, Dr.-Karl-Dorrek-Straße 30,3500 Krems, Trakt Y, Erdgeschoß