Mechanisms of hepatocarcinogenesis
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and the second leading cause of cancer-related death in men worldwide with rising incidence in many parts of the world including central Europe. Basic mechanisms of hepatocarcinogenesis are studied using mouse models (i.e. Mcl1hep mice and their intercrossings; diet models), complemented by correlative studies to human liver diseases. A major focus is the study of tumorigenesis as a result of persistent apoptotic cell death and regeneration, an etiology-independent hallmark of chronic liver diseases with tissue destruction. A special interest exists in the increasingly important metabolic disorders of the liver, i.e. non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and NASH-driven HCC.
Publications: Weber et al. (2010) Hepatology (see also editorial: Jost & Kaufmann, (2010) Hepatology); Wolf et al. (2014) Cancer Cell
Comprehensive characterization and classification of murine hepatocellular carcinoma (HCC) by comparing mouse models of hepatocarcinogenesis with human HCC
Molecular characterization of tumors is a prerequisite for classification and targeted molecular therapy. Liver tumors of several murine models are comprehensively characterized on morphological and immune phenotypical level (whole slide virtual imaging and recording) and genetically (aCGH, mutational analysis) aiming to develop a classification of murine tumors. A particular focus is the comparability and applicability to human liver tumors. A special interest lies in characterizing HCC intratumor heterogeneity which has implications to tumor classification approaches and molecular targeted therapy.
Publications: Friemel et al. (2015) Clinical Cancer Research (see also highlight of this issue and editorial: Nault & Villanueva, (2015) Clinical Cancer Research)
Clinico-pathological characterization of Hepatitis E virus (HEV)
Hepatitis E virus (HEV) infection recently is emerging in Western Europe. Clinical and histo-pathological diagnosis of HEV infection can be challenging, in particular in patients under immunosupression or in deliniation to drug-induce liver-injury (DILI). HEV infection is characterized clinico-pathologically, and diagnostic tests for routine application are developed aiming to improve histopathological diagnosis of HEV infection.
Publications: Protzer et al. (2015) Mod Pathol; Chijioke et al. (2015) Frontiers in Medicine, Pathology
Intestinal tract apoptosis and carcinogenesis
Apoptosis of intestinal epithelial cells is a hallmark of chronic inflammatory bowel diseases (IBD) and also occurs as drug-induced damage of the GI tract. The significance of chronically elevated intestinal apoptosis for intestinal inflammation and tumorigenesis is studied in mouse models, as well as clinico-pathological characteristics of human apoptosis-related diseases in the intestinal tract.
Publications: Soldini et al. (2014) J Clin Pathol; Weber & Marques Maggio (2013) Pathobiology