“Multiomic integration reveals tumoral heterogeneity of lipid dependence within lethal Group 3 medulloblastoma.”

The paper analyzes hundreds of samples the using the Illumina EPIC methylation array  to analyze and compare DNA methylation in models owned by brain tumor mouse model development experts from around the world. This major project took five years from sample collection, and one of the lead authors is Tuyu Zheng (currently a postdoctoral researcher at St. Jude Children’s Research Hospital), a former doctoral student whom Professor Kawauchi supervised when he was a PI in Germany. Lab members Wang (graduate student), Shiraishi (PhD graduate) and Kawauchi (PI) are coauthors. Read it here.

Prof. Kawauchi and graduate student Wang co-authored this article at the request of our friend Michael Goldstein at Duke University to share the somatic mutation-based mouse model generation techniques we utilize in medulloblastoma research.

Read it here.

Graduate student Xiao demonstrated that SHTN1 promotes migration of human glioblastoma cells using brain organoids. These organoids were established in collaboration with Prof. Yoshitsugu Aoki at NCNP (Xiao et al., in preparation). 

The research was featured in Yahoo! News JP.

Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation

Pediatric brain tumors, the most devastating cancers affecting children, are believed to originate from neural stem/progenitor cells in developing brain. In precise timing and specific regions during the brain development, chromatin deregulation plays crucial roles in redirecting normal neuronal differentiation pathways toward tumorigenesis. Indeed, epigenomic abnormalities are thought to be more important for brain tumor formation especially in children than adults, as pediatric brain tumors generally exhibit fewer genetic mutations compared to adult brain tumors. Given the small number of mutations, targeting such limited alterations involved in cancer epigenomes is expected to be more effective in pediatric brain tumors. The mechanisms of cancer epigenomes include mutation or dysregulation of chromatin remodelers, histone modifiers, histones themselves, and DNA methylation enzymes. Furthermore, genomic rearrangements and/or higher-order chromatin topology also contribute to these epigenomic mechanisms. These mechanisms are commonly observed in various types of pediatric brain tumors. However, alterations in chromatin regulatory factors differ across tumor types, reflecting the unique epigenetic landscapes shaped by their tumor origins. Accordingly, clarifying their functional similarities and differences across tumor types could offer valuable insights for finding new therapeutic strategies. Thus, this review article focuses on elucidating how pediatric brain tumors arise from epigenomic deregulation and what epigenetic molecules or mechanisms could serve as therapeutic targets.

Read it here.

Prof. Kawauchi presented “Conditional expression and activation of DREADDs reveals novel impact of neuron-tumor communications on brain tumor progression” at Neuro2024 (Fukuoka). This is a collaborative study with Prof. Naofumi Uesaka from Tokyo Medical and Dental University, focusing on elucidating the relationship between brain tumors and neural activity. Now, the fields of brain tumors and neuroscience should be integrated, requiring more multifaceted analysis. On the other hand, such unique research is expected to reveal new mechanisms of tumor progression!

With the opportunity provided by the Department of Neurophysiology at Tokyo Women’s Medical University (Professor Mariko Miyata), Professor Kawauchi presented his recent findings on brain tumor research and discussed future developments in the field. We extend our heartfelt gratitude to audience at Tokyo Women’s Medical University, Professor Mariko Miyata, and coordinator Dr. Hisako Nakayama for their participation and support.