Errors in mitosis as a source of inherited (epi)genetic instability

Stamatis Papathanasiou, Group Leader at the Institute of Molecular Biology (IMB), Mainz, Germany, was chosen for the EACR – Mark Foundation – Pezcoller Foundation Rising Star Award based on the high quality of his project proposal on ‘Mechanisms of cellular response to errors in mitosis: a new, non-genetic approach to an old question’.

Stamatis studied Molecular Biology and Biotechnology in the Biology department of the University of Crete in Greece. He then received his Master’s and PhD in Molecular Medicine from the National and Kapodistrian University of Athens in 2015. He was awarded the “Fotis Kafatos Award of Excellence” for his PhD studies deciphering how cardiomyocyte cytoskeleton is dysregulated in heart failure. He then moved to Boston to continue his research in Dana Farber Cancer Institute and Cell Biology department of Harvard Medical School, where he focused on understanding basic mechanisms of tumorigenesis that are mediated by errors in mitosis and the generation of abnormal nuclear structures. A prominent example of such structures is the micronuclei, aberrant nuclear formations that form as a result of mitotic errors and are prevalent in cancer. Stamatis first showed that mitotic errors and micronuclei formation is a previously unknown on-target side effect of CRISPR-Cas9 human genome editing and that this can lead to genomic instability. He then developed new systems to study the transcription and chromatin state of these abnormal structures.

With his recent work Stamatis showed that they can also generate heritable alterations in transcription and chromatin state. This work suggested that abnormal nuclear structures from errors in mitosis are a new source of epigenetic instability and transcriptional heterogeneity, which opens new fascinating directions on uncovering novel mechanisms of tumorigenesis with potential therapeutic implications.