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Kliniken &… Institute Pathologie Allgemeine… Forschung Arbeitsgruppen AG Longerich

Longerich lab

Research focus

In most cases carcinogenesis represents a multi-step process with morphologically defined premalignant lesions. In case of hepatocellular neoplasia, these are called dysplastic nodules and precede the development of hepatocellular carcinoma. Furthermore, recent evidence suggested that intrahepatic cholangiocarcinoma, a tumor thought to be derived from the biliary tree, may also develop from hepatocytes.

Although the underlying chronic liver diseases (mainly chronic Hepatitis B and C virus infection, chronic alcohol abuse, metabolic syndrome, genetic hemochromatosis) inducing the development of hepatocyte-derived liver tumors are well defined, the molecular alterations promoting certain steps of tumor initiation and progression remain elusive. In addition, the impact of the cancer-associated stroma both regarding the biological behavior as well as the response to treatment remain elusive.

Our research aims at defining driver genes leading to the evolution and progression of human liver carcinomas and to identify mechanisms affecting liver cell plasticity and tumor phenotype. Additionally, we aim at the identification of molecular markers that may be useful for diagnosis, prediction of therapy response and/or therapeutic targeting.

We use comprehensive profiling approaches at DNA and RNA level to identify potential driver genes in phenotypically defined lesions of liver carcinogenesis. These are validated in human samples by molecular pathological approaches (real-time RT-PCR, Western immunoblot, immunohistochemistry, ChIP, Sanger and next generation sequencing) and the resulting candidates are validated in vitro using transfections/infections (siRNA, shRNA, cDNA) as well as CRISPR/Cas9-mediated genomic engineering of liver cell lines. Finally, in vivo analyses are performed using mosaic mouse models.

Team

Thomas Longerich, MD

thomas.longerich(at)med.uni-heidelberg.de

Rossella Pellegrino, PhD

rossella.pellegrino(at)med.uni-heidelberg.de

Noujan Ganjian, PhD candidate

noujan.ganjian(at)med.uni-heidelberg.de

Ariane Neumann, technician

ariane.neumann(at)med.uni-heidelberg.de

Jasmin Krömer, technician

jasmin.kroemer(at)med.uni-heidelberg.de

 

Link to publications