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Professor Daichi Inoue

Cancer Pathology

The leaders of our laboratory can be traced back to Professor Aihiko Sata of the First Department of Pathology, who has been followed by distinctive Professors Miyakichi Murata, Ryojun Kinoshita, Toru Miyaji, Hajime Kitamura, Yukihiko Kitamura, and Toru Nakano up to the present. Originating from Kobe, our laboratory will leverage the rich resources of Osaka University to further develop our research to unravel cancer mechanisms.

Exploration of unrecognized mechanisms that separate normal cells from tumors and their therapeutic application

Cancer ensures its survival with intricate and precise strategies. To understand and confront cancers, which could be the fate of humanity, it is essential to demonstrate the vulnerability of cancer cells, rooted in the control mechanisms of normal stem cells. Our laboratory has uncovered crucial insights into how genetic information undergoes distortion at post-transcriptional RNA levels, exemplified by splicing mechanism failures. Additionally, we’ve observed cancer cells manipulating their microenvironment to their advantage through extracellular vesicles. Our studies, particularly focused on hematologic malignancies like leukemia, reveal how factors involved in chromatin remodeling, transcription, and signal transduction undergo modulation or loss of function due to aberrant RNA splicing, leading to dysregulation of vital genes. These findings shed light on previously unknown regulatory mechanisms surrounding the central dogma of molecular biology.

The origins of these phenomena lie not only in alterations to trans-acting factors, such as mutations and altered expression of RNA-binding proteins but also in cis-acting elements, including mutations of intron sequences, spanning various cancer types. Furthermore, cancer cell vulnerability manifests across a spectrum of post-transcriptional mechanisms, from RNA methylation to translation. We aim to conduct pathological analyses of this vulnerability with precision surpassing genome/chromosome-level “information rewriting.”

In the Laboratory of Cancer Pathology, we are dedicated to embracing the “Pathology of the New Era,” illuminating the future of medicine through comprehensive evaluations spanning basic and clinical approaches. Our research spans multicellular systems, examining genomic mutation, post-transcriptional regulation, chromatin control, metabolic reprogramming, and cell death dynamics. Additionally, we investigate the pathology of cancer, exploring connections between precancerous lesions and multiple organs, evolutionary conservation and carcinogenesis, and the interplay of carcinogenesis and ontogeny, fostering cross-disciplinary studies. We aim to address longstanding questions through innovative approaches and tackle fundamental inquiries, such as “Where did cancers come from, and where are they going?” using multicellular systems and time concepts. To promote these efforts effectively, we will employ screenings and cell lineage analyses using state-of-the-art single-cell analysis platforms, genome editing, and base editing techniques. Moreover, we are committed to fostering young researchers who will lead the next generation through innovative studies in cancer pathology.