We are excited to announce our next CRC 1530 seminar featuring Prof. Heinz Jacobs PhD, research group leader at the Netherlands Cancer Institute.
Title: Epigenetically Programmed Identity Crisis to Combat Diffuse Large B Cell Lymphoma
When: Tuesday, 15 September 2026, 1:15 pm
Where: Center of Integrated Oncology, seminar room 3+4 (building 70, Kerpener Str. 62, 50937 Köln, UKKöln Navi)
Host: Ron Jachimowicz,
MPI for Biology of Ageing / Dept. I of Internal Medicine, University of Cologne
Abstract:
The establishment and maintenance of germinal center (GC) B‑cell identity rely on a finely tuned epigenetic network centered on the histone methyltransferases DOT1L and EZH2. Across normal and malignant B‑cell contexts, these enzymes safeguard a pro‑proliferative GC transcriptional program while enforcing repression of anti‑proliferative plasma cell (PC) differentiation circuits. In primary B cells, DOT1L establishes an epigenetic barrier that preserves B‑cell naivety, enables GC formation, and prevents premature acquisition of PC characteristics. In GCB‑DLBCL, this dependency becomes amplified: DOT1L and EZH2 cooperatively maintain malignant GC identity by shaping PRC2‑mediated repression and stabilizing ncPRC1‑dependent H2AK119ub1 deposition, thereby silencing PC signature genes. Combined inhibition of DOT1L and EZH2 disrupts this cooperative repression, leading to de-repression of PRC1/2 targets, suppression of MYC‑driven proliferation programs, and induction of partial PC‑like differentiation. This coordinated collapse of GC identity constitutes an epigenetically programmed identity crisis (EPIC), a therapeutically exploitable state that halts tumor outgrowth in vivo. Together, these studies define DOT1L and EZH2 as central architects of GC fate control and highlight the therapeutic potential of targeting their cooperative chromatin‑regulatory functions to rewire malignant B‑cell identity.
Prof. Heinz Jacobs is a senior group leader at the NKI-AVL whose research focuses on somatic hypermutation, lymphocyte development, DNA damage tolerance, and epigenetic programming. After earning his PhD at NKI-AVL and completing postdoctoral research in the division of Klaus Rajewsky, Institute for Genetics at the University of Cologne, he led a research group at the Basel Institute for Immunology before returning to NKI-AVL in 2002 to study the mechanisms of immunity, immunotherapy, and lymphoma treatment.
This is a hybrid seminar. If you are unable to attend in person, please register for the online meeting on Zoom.
We look forward to to seeing you there!
