atb – Applied Tumor Biology
The Department of Applied Tumor Biology (ATB) at Heidelberg University Hospital’s Institute of Pathology is an interdisciplinary, translationally-oriented research laboratory. We aim to decipher basic molecular mechanisms that contribute to the development of cancer.
ATB is predominantly focusing on cancers caused by persistent human papilloma virus infections and those triggered by loss of DNA mismatch repair functions.
ATB is affiliated with Heidelberg University Hospital and the German Cancer Research Center (DKFZ). We are also part of the Molecular Medicine Partnership Unit (MMPU) of the European Molecular Biology Laboratory (EMBL) in Heidelberg.
The aim of the ATB’s team is to identify and understand molecular mechanisms that turn normal somatic cells into cancer cells and to derive novel concepts for the development of diagnostic markers as well as therapeutic targets from that research.
Human papilloma viruses (HPVs) cause widespread infections of the skin and mucosal surfaces and in some instances pre-cancer and cancer predominantly of the anogenital region and the oropharynx. About 5 % of all cancers that occur worldwide are accountable to persistent HPV-infections.
Research over the past 30 years revealed that the oncogenic activity of HPVs is mediated by two oncogenes (E6 and E7) that are required to induce and maintain their carcinogenic function.
ATB is actively studying the mechanism why these oncogenes become activated in distinct human epithelial cells. ATB further developed biomarkers to highlight such HPV transformed cells and is devloping therapies that block the activity and function of the HPV oncogenes.
Every living cell has a set of proteins constituting the DNA Mismatch Repair (MMR) system. The MMR system is responsible for correcting nucleotide mismatches occurring in the DNA during cell replication.
Short repetitive sequences, so-called microsatellites, are particularly prone to accumulation of such mismatches. Therefore, when the MMR system does not function, insertion-deletion mutations accumulate at microsatellites causing Microsatellite Instability (MSI) and leading to cancer development. MSI has dramatic consequences on the pathogenesis and immunogenicity of cancer cells, opening possibilities for immunotherapy and immune prevention of MSI cancers.
Sugar molecules constituting glycans provide the proteome of cells with enormous diversity, thereby being capable of altering biological properties of proteins. In cancer, cells have a completely different glycan and glycoprotein profile, which can be used as basis for designing novel approaches for cancer treatment and diagnostics.
Moreover, due to high energetic demands, consumption of sugars also differs between cancer and normal cells. Cancer cells consume substantially more glucose, therefore glucose dependence represents the Achilles’s Heel of cancer and can be targeted by specific substances that inhibit metabolic pathways in cancer cells.