ABSTRACT

Every cell in our body must not only acquire a specific identity during development but also hold that line for a lifetime — often against constant pressure to drift, dedifferentiate, or transform. How cells achieve this stability sits at the heart of developmental biology, regenerative medicine, and cancer research. While decades of work have illuminated the activators that switch on cell fate programs, an equally vital layer of control has remained underappreciated: the active repression of alternative fates that keeps cells from slipping into the wrong identity.

In this talk, I will discuss how dedicated transcriptional repressors act as molecular guardians of cellular identity in both the healthy and diseased human brain, as well as in aggressive cancers such as glioblastoma and liver carcinoma. Combining human stem cell–derived neurons, brain organoids, and in vivo models with single-cell multi-omics, computational modeling, and cell fate engineering, we show that the loss of such repressors unlocks aberrant gene programs that drive neurodevelopmental disorders, fuel tumor progression, and undermine reprogramming strategies. Conversely, restoring or enhancing repressor activity can re-establish identity, suppress malignancy, and reveal new therapeutic opportunities.

Together, these findings point to an emerging paradigm in which silencing the wrong fate is as fundamental as activating the right one. By learning how cells hold the line, we open concrete avenues toward regenerative therapy and precision oncology.

BIOSKETCH

Dr. Moritz Mall is a division head at the German Cancer Research Center (DKFZ) and founding member of the Hector Institute for Translational Brain Research (HITBR). His lab studies cellular plasticity—how cells change identity—a process central to cancer and developmental disorders. Using stem cell and organoid models of brain and liver, his team investigates the genetic and epigenetic control of disease transitions to discover new treatments.

Dr. Mall studied in Munich and Zurich, earned his PhD at EMBL Heidelberg, and trained at Stanford University as a German Research Foundation postdoctoral fellow. He has received several awards, including an ERC Starting Grant and the Hella Bühler Prize for cancer research.

In addition to publishing in leading journals such as Nature, Dr. Mall is committed to outreach and translational science. He actively supports families affected by rare autism-associated disorders and works closely with patient communities. His team’s research has already contributed to compassionate-use therapies, showing how patient-driven science can help bring targeted treatments to the clinic.