Kosuke Funato
My research focuses on glioblastoma, the most aggressive brain tumor and one of the most lethal tumor types in both adults and children. I received my Ph.D. for my research on glioblastoma stem-like cells and have been involved in glioblastoma research for more than 10
years.
In the recent years, I have been studying recurrent histone mutations found in pediatric glioblastoma: histone H3K27M and G34R/V mutations. It has been shown that these two types of histone mutations define clinically and molecularly distinct subtypes of glioblastoma.
However, little was known about their cell types of origin and the precise mechanisms by which the histone mutations transform particular cell types. To address these questions, I developed a new tumor model system based on human embryonic stem cells (hESC) (Funato et al., Science 2014; Funato et al., Cell Stem Cell 2021). Given that hESCs can be differentiated into various neuronal cell types by chemically-defined protocols, this system enables us to interrogate the role of each single mutation, or combination of mutations, in defined cell populations. Our
studies demonstrate that the hESC-based tumor model is a powerful system to interrogate the genetic, molecular, and cellular mechanisms underlying gliomagenesis. In combination with other methodologies, such as patient-derived cell lines and genetic mouse models, our lab aims
to identify the subtype-specific mechanisms of gliomagenesis and develop tailor-made therapies for patients suffering from this devastating disease.