Mechanisms of DNA Repair
The integrity of our genome needs to be preserved to ensure the faithful passage of genetic information to our progeny. An extensive network of DNA repair pathways ensure that the consequences of DNA damage are held to a minimum. Defects in DNA repair pathways thus promote genome instability and are a central contributor to ageing and carcinogenesis
Supporting the importance of genome stability on an organismal level, human genome instability syndromes frequently share clinical features of premature ageing and ageing-associated diseases, including increased cancer susceptibility, neurodegeneration, and immunodeficiency. For example, the identification of Ataxia-telangiectasia—the disease underlying germline ATM mutations— contributed significantly to our mechanistic understanding of the DNA damage response, as well cancer- and ageing-related pathways. Somatic mutations in ATM are further commonly found in mantle cell lymphoma, a mature B-cell lymphoma typically affecting the elderly, for which mechanism-based therapies are scarce with poor overall treatment outcome.
Our research aims to provide a better understanding of the relationship between genome maintenance, ageing, and cancer, in an interdisciplinary approach. We dissect defects in DNA repair pathways in patients with genome instability syndromes and in patients suffering from mantle cell lymphoma, providing a rich and unparalleled opportunity to uncover novel pathways in a meaningful organism. We utilize tools involving biochemistry, cell biology, and computational biology, and transfer these findings to modern mouse genetics, that will ultimately lead to genetically-informed therapies for patients suffering from cancer and ageing associated diseases.
Selected Publications Jachimowicz
Third party funding
- E.I. Stiftung Kölner Krebsforschung
- Hilde-Kopp Stiftung