Inflammation induced tissue damage

Junior Group Mathias Heikenwälder

The causal relationship between chronic inflammation, tissue damage, fibrosis and carcinogenesis is well established by epidemiological studies. Various etiologies, including chronic alcohol consumption, chronic drug abuse, autoimmune disorders, toxins (e.g. aflatoxin B), infections with viruses (e.g. Hepatitis B and Hepatitis C virus) or bacteria (e.g. Helicobacter pylori) can lead to chronic inflammation, tissue damage and carcinogenesis. Aberrant expression of cytotoxic cytokines by immune but also non-immune cells is thought to be critically involved in the initial induction of inflammation and its progression towards a chronic state.
 
Our laboratory aims at understanding the signaling pathways of inflammation (e.g. cytokines and chemokines), apoptosis and proliferation as well as tries to unravel the cellular mechanisms responsible for induction and maintenance of chronic inflammation, finally leading to tissue destruction and cancer.

One main focus of this laboratory is to elucidate the patho-mechanisms of Hepatitis B (HBV) and Hepatitis C (HCV) viruses, by far the most common cause of chronic hepatitis in humans. HBV and HCV infections are frequently associated with hepatocellular carcinoma, the most prevalent primary human liver cancer and fifth most frequent cause of cancer related death. However, the cellular and molecular mechanisms driving hepatitis-induced liver cancer remain elusive.
 
Our work involves the generation of mouse models for chronic inflammatory disorders in different organs (e.g. pancreas, muscle, CNS, liver) as well as work with human tissue and body fluids derived from healthy as well as diseased individuals (e.g. HCV or HBV infected patients).

We are also interested in an in-detail analysis and characterization of hepatocellular carcinoma and other solid tumors by combining and correlating immunohsitological with genetic (array comparative hybridization analysis) and transcriptional changes (micro-array).

Another focus of the laboratory is to understand the mechanisms of tumor cell metastasis and how this process is controlled on a cellular and molecular level.

Besides we aim at translating our research into a clinical setting and therefore are currently initiating a first clinical trial in collaboration with Biogen Idec, the Clinical trial center Zürich and the TUM/Helmholtz Institute.


Funding

  • Helmholtz Young Investigator Group award
  • European Research Council (ERC)
  • SFB Transregio (SFBTR-p0'36)
  • The Hofschneider foundation for Bio-medical Research