Contact

 

Prof. Dr. med. Thorsten Zenz
Phone: +49 6221 565931

E-mail: thorsten.zenz@nct-heidelberg.de

 

 

Molecular Therapy in Haematology and Oncology

DKFZ
 
 
 

The main focus of our group is to 1) advance our understanding of molecular and genetic lesions in the pathogenesis of lymphoma subtypes and 2) use this understanding to exploit it therapeutically.
Over the last years, we have contributed to the understanding how genetic lesions contribute to lymphomagenesis. One particular focus of the group has been to define the role of the p53 pathway and particular mutant p53 in lymphoma. In addition to the assessment of molecular and clinical consequences of these genetic lesions, we focus on the identification of alternative drivers of disease traits.
To develop rational and biology-based ways for patient benefit from advances in molecular understanding and targeted drug treatment, we pursue an innovative strategy based on the comprehensive mapping and understanding of individual cancers’ vulnerability to compounds, pathway inhibitors and drugs as well as genome-wide silencing triggers (RNAi, CRISPR).

 

We systematically map pathway sensitivity (and resistance) of primary tumor cells ex vivo using diverse and relevant compound library across leukemia and lymphoma. By analysing response patterns of sensitivity and resistance we group tumors functionally, by response phenotype. In parallel, we directly associate and understand drug actions and their variability by investigating the underlying (causative) genetic or epigenetic changes, critical pathway activation, metabolic changes, the biology of the cell of origin and the microenvironment.
Following the identification of clinically actionable vulnerabilities on primary tumors, we will mechanistically validate these with in vitro (incl. RNAi) and in vivo models and develop rational starting points for clinical development. We classify disease based on pathway sensitivity and the systematic understanding of underlying molecular networks.
We combine local expertise and cooperation with strong national and international cooperation (DKTK, DCLLSG, ERIC, CCE) to develop competitive clinical and research platforms to specifically focus on lymphoproliferative disease (LPD).

Team

  • Thorsten Zenz, MD
  • Sascha Dietrich, MD (Group leader, BMBF/MMPU group)
  • Jennifer Hüllein, PhD Student
  • Alexander Jethwa, PhD Student
  • Vladislav Kim, student
  • Marina Lukas, MD student
  • Leopold Sellner, MD
  • Kwang Seok Lee, PhD Student
  • Mikołaj Słabicki, PhD
  • Kasia Tomska, MD student
  • Lena Wagner, Technician
  • Tatjana Walther, Technician

Key publications

  1. Oakes CC, Seifert M, Assenov Y, Gu L, Przekopowitz M, Ruppert AS, Wang Q, Imbusch CD, Serva A, Koser SD, Brocks D, Lipka DB, Bogatyrova O, Weichenhan D, Brors B, Rassenti L, Kipps TJ, Mertens D, Zapatka M, Lichter P, Döhner H, Küppers R, Zenz T, Stilgenbauer S, Byrd JC, Plass C. DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia. Nat Genet. 2016 Mar;48(3):253-64. doi: 10.1038/ng.3488.

  2. Dietrich S, Hüllein J, Lee SC, Hutter B, Gonzalez D, Jayne S, Dyer MJ, Oleś M, Else M, Liu X, Słabicki M, Wu B, Troussard X, Dürig J, Andrulis M, Dearden C, von Kalle C, Granzow M, Jauch A, Fröhling S, Huber W, Meggendorfer M, Haferlach T, Ho AD, Richter D, Brors B, Glimm H, Matutes E, Abdel Wahab O, Zenz T. Recurrent CDKN1B (p27) mutations in hairy cell leukemia. Blood. 2015 Aug 20;126(8):1005-8.

  3. Oakes CC, Claus R, Gu L, Assenov Y, Hüllein J, Zucknick M, Bieg M, Brocks D, Bogatyrova O, Schmidt CR, Rassenti L, Kipps TJ, Mertens D, Lichter P, Döhner H, Stilgenbauer S, Byrd JC, Zenz T, Plass C. Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia. Cancer Discov. 2014 Mar;4(3):348-61. doi: 10.1158/2159-8290.CD-13-0349.

  4. Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med. 2012 May 24;366(21):2038-40.

  5. Zenz T, Mertens D, Küppers R, Döhner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2010 Jan;10(1):37-50.