Nuclear structures formed by liquid-liquid phase separation are known to regulate various cellular functions. Recently, it has been elucidated that the disruption of liquid-liquid phase separation leads to the development of various diseases, including neurodegenerative disorders. To elucidate the functions of nuclear structures, we have established antibody-based in situ biotinylation labeling method and comprehensively identified the components of several nuclear structures including nucleoli, γH2AX and Cajal bodies. Furthermore, public databases were also used to elucidate the interactome among the identified proteins, genomic DNAs and RNAs in Cajal bodies. The results revealed that the interaction between newly transcribed RNAs and RNA-binding proteins may play an important role in the formation of Cajal bodies. This study may shed light on the mechanism of nuclear structure formation and its disruption in the pathogenesis of diseases.

In Japan, approximately 380,000 people die from cancer each year. Despite the development of various treatments and anticancer drugs, a significant challenge in cancer therapy is that cancer eventually acquires resistance to these treatments. Numerous cancer cells are generated during cancer proliferation, exhibiting slight variations in gene expression patterns, leading to heterogeneity. This heterogeneity results in the emergence of cancer cells resistant to external stimuli such as anticancer drugs. Our research has focused on cancer stem-like cells (CSCs) and their expression of stem cell-related transcription factors. These transcription factors contribute to tumor growth, treatment resistance, and immune evasion. Additionally, we have utilized DNA barcode technology and the CRISPR/Cas9 system to analyze the emergence of CSCs and the functions of stem cell-related transcription factors within cancer cell populations. This has provided new insights into the relationship between the expression of these transcription factors and cell behavior. In this article, we will introduce our recent research findings.

Proteogenomics is a genomic approach from the perspective of proteomes. It started 30 years ago, but since then, genome and proteomic analyses have continued to develop their respective technologies at a tremendous pace, and have finally reached the horizon we originally expected. Here, I begin with the relationship between the genome and proteome at the dawn of time, describe the achievements of proteomics based on current genomic information, and discuss future prospects. In particular, I will focus on the development history and current status of human proteome analysis technology, and touch on the actual application status of the technology. Will this combination of innovations in measurement technology bring about a new paradigm in our views of life? Will it give us wisdom to overcome the many challenges we face that we have to think about on a global and human scale? We hope that proteogenomics can contribute to solving these challenges.