Another outstanding PhD defense this year! Many congratulations to Dr. rer. nat. Sofia Gialesaki, who graduated from the HBRS Molecular Medicine PhD program with top honours (summa cum laude). Her thesis is titled “Deciphering the deregulated complex transcription network in Down syndrome myeloid leukemia”.
Down syndrome myeloid leukemia (ML-DS) is thought to originate in the fetal liver, where the interplay between fetal hematopoiesis, trisomy 21, and truncating mutations in GATA1 (GATA1s) causes transient abnormal myelopoiesis (TAM). The first part of Sofia’s PhD work aimed to understand the effects of GATA1s on hematopoiesis at different stages of human development. Utilizing hematopoietic stem and progenitor cells (HSPCs) of different ontogenies, Sofia showed that induction of GATA1s resulted in a transient hyperproliferation of megakaryocytic progenitors – recapitulating the TAM phenotype – in HSPCs of fetal, but not neonatal or adult, origin (view the paper here).
The second part of Sofia’s PhD work centers on identifying oncogenic factors on human chromosome 21 that contribute to ML-DS, and was the topic of her recent Presidential Symposium talk at the EHA conference. In short, the equilibrium between the RUNX1 isoforms was found to be disrupted in ML-DS blasts compared to normal HSPCs, and in a series of in vitro and in vivo experiments, Sofia demonstrated that this dysregulation synergizes with GATA1s to drive leukemogenesis. She is currently staying on as a postdoc to further consolidate this story.