DNA damage & Cancer

Dysfunction of the DNA damage response is a driving force for genome instability and cancer. In childhood cancers, inherited mutations in cancer predisposition genes substantially contribute to cancer development and was linked to specific cancer-predisposing syndromes (CPS). Numerous CPS including Li-Fraumeni syndrome (LFS), Li-Fraumeni like syndrome (LFLS) and Fanconi anemia (FA)/Breast Cancer Associated (BRCA) have been described. In general, LFS and LFLS patients harbor germline mutations in genes regulating the tumor suppressor p53 pathway, while FA/BRCA patients harbor mutations in genes required for DNA double-strand break (DSB) repair. Interestingly, a substantial part of FA, LFS and LFLS patients do not harbor the known homozygous mutations in the genes linked to the respective CPS. Consequently, the mechanisms driving the CPS in those patients remain unclear. In this collaborative project, we used whole-exome sequencing (WES) of parents-children trios to identify germline mutations in children with cancer. Our bioinformatic analysis revealed a set of novel combined heterozygous mutations in the FA/BRCA and the LFS/LFLS pathway as well as in genes coding for the DNA damage signaling kinases ATM, ATR and HIPK2 in the germline of children with cancer.

Research website

Positions held

  • Since 2018: W3-Professor & Chair of Toxicology, Institute of Toxicology, University Medical Center (UMC), Mainz; Director, Institute of Toxicology, University Medical Center (UMC), Mainz
  • 2008 - 2018: Permanent Group Leader Position, DKFZ, Heidelberg
  • 2006 - 2018: Head of Research Group “Cellular Senescence”, German Cancer Research Center (DKFZ), Heidelberg
  • 2004 - 2005: Research Group “Molecular Ageing Research”, German Center for Research on Ageing (DZFA), University of Heidelberg

Education

  • 2016: Habilitation and venia legendi for Biochemistry & Molecular Biology , Faculty of Biology, University of Heidelberg 
  • 2000 - 2004: Postdoctoral research with Prof. Hans Will, Heinrich-Pette-Institut, University of Hamburg
  • 2000: PhD (summa cum laude), University of Heidelberg
  • 1997 - 2000: PhD studies with Prof. Wulf Dröge, DKFZ Heidelberg
  • 1997: Diploma in Biology, University of Heidelberg
  • 1991 - 1997: Studies of Biology, University of Heidelberg

Selected publications by Thomas Hofmann

Liebl MC, Moehlenbrink J, Becker H, Raddatz G, Abdeen SK, Aqeilan RI, Lyko F, Hofmann TG (2021) DAZAP2 acts as specifier of the p53 response to DNA damage. Nucleic Acids Res, 49(5):2759-2776 Link

Rodríguez-Paredes M, Bormann F, Raddatz G, Gutekunst J, Lucena-Porcel C, Köhler F, Wurzer E, Schmidt K, Gallinat S, Wenck H, Röwert-Huber J, Denisova E, Feuerbach L, Park J, Brors B, Herpel E, Nindl I, Hofmann TG, Winnefeld M and Lyko F (2018) Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin. Nat Comm, 9:577 Link

Conrad E, Polonio-Vallon T, Meister M, Matt S, Bitomsky N, Herbel C, Liebl M, Greiner V, Kriznik B, Schumacher S, Krieghoff-Henning E, and Hofmann TG (2016) HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism. Cell Death Differ, 23:110-122 Link

Ucar O, Kaiyong Li, Dvornikov D, Kreuz C, Timmer J, Matt S, Brenner L, Smedley S, Travis MA, Hofmann TG, Klingmüller U and Kyewski B (2016) A thymic epithelial stem cell pool persists throughout ontogeny and is modulated by TGF-ß. Cell Reports, 17:448-457 Link

Ucar A, Ucar O, Klug P, Matt S, Brunk F, Hofmann TG* and Kyewski B* (2014). Adult thymus contains FoxN1- epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages. Immunity, 41:257-269 (*indicates joint contribution) Link