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Computational Biology Group／Inter-Institute Cooperative LaboratoriesYamashita Laboratory
(Cancer Medical Informatics Group, NCC)

Recruit status

We are treating real data directly related to clinical practice.

Our laboratory, the Department of Translational Informatics at the Exploratory Oncology Research & Clinical Trial Center, National Cancer Centre Hospital East, is located near the Kashiwa Campus of the University of Tokyo. Our primary focus is conducting research that aims to uncover the actual mechanism of cancer and develop treatments by analyzing bioinformatics technology. We strive to make 'translational informatics,' which uncovers the fundamental mechanism joined by multilayer omics data accumulated at the National Cancer Centre with bioinformatics.

Research
keywords
Bioinformatics, transcriptional regulation, translational regulation, metagenomics, multilayer omics analysis, cancer genomics, AI
Integrated analysis of multi-omics data related to cancer

Reliable clinical information obtained from clinical trials and other precise sources is crucial for improving cancer treatment. With the increasing amount of cancer related information obtained from whole exome analysis, transcriptome analysis, and other methods, it is becoming more challenging to manage and integrate this data. In recent years, information on spatial omics analysis, which combines tissue images with one-cell-level analysis, has also been increasing. To extract novel knowledge from these data, it is necessary to integrate not only existing medical and biological knowledge but also information science knowledge called bioinformatics. Our laboratory aims to use bioinformatics to extract medical and biological information.

Analysis for transcriptional and translational regulation

Multi-layered omics analyses, such as genomic, transcriptomic, and epigenomic, are essential for studying cancer mechanisms and drug effects. These analyses use patient specimens, animal, and cellular model samples. In cancer, aberrant transcription and translation are known to occur, making it necessary to use information on precise transcription start sites and other omics data. Our laboratory is focusing on, for example, transcriptional regulation in cancer cells under radiotherapy by analyzing these data. We are also studying non-coding RNAs, building cancer-specific databases, and exploring their potential for translation.

Metagenomic analysis

Microbiome information is now accumulating, with comprehensive studies of the microbiota present in human bodies. The link with cancer is also attracting attention, and it has been reported that the response to immune checkpoint inhibitors and some molecularly targeted drugs is associated with the microbiota. Our laboratory aims to define a new indicator of how abundant the microbiota is, which will allow for more accurate estimation for specimen Furthermore, we aim to construct a system that can estimate the intestinal microbiota using faeces and other specimens from actual cancer patients and predict treatment efficacy using AI technology.

Construction of a Database for Clonal hematopoiesis of indeterminate potential (CHIP) in Japanese.

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the phenomenon where specific genetic mutations, often found in hematological tumors such as leukemia, are also found in blood cells from healthy individuals. These mutations are generally not immediately problematic but can lead to erroneous decisions, especially in some recent cancer genome panel tests called liquid biopsies. In collaboration with the Tohoku University Tohoku Medical Megabank Organisation, our laboratory is developing a Japanese-specific CHIP database, CHIPS-DB, by using large-scale Japanese genome information.

Recent research results/papers
  1. Shitara K, Muro K, Watanabe J, Yamazaki K, Ohori H, Shiozawa M, Takashima A, Yokota M, Makiyama A, Akazawa N, Ojima H, Yuasa Y, Miwa K, Yasui H, Oki E, Sato T, Naitoh T, Komatsu Y, Kato T, Mori I, Yamanaka K, Hihara M, Soeda J, Misumi T, Yamamoto K, Yamashita R, Akagi K, Ochiai A, Uetake H, Tsuchihara K, Yoshino T. Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. Nat Med. 2024 Mar;30(3):730-739. doi: 10.1038/s41591-023-02791-w. Epub 2024 Feb 12. PMID: 38347302; PMCID: PMC10957476.
  2. Oyoshi H, Du J, Sakai SA, Yamashita R, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Nakamura Y, Kojima M, Suzuki A, Zenkoh J, Tsuchihara K, Akimoto T, Shibata A, Suzuki Y, Kageyama SI. Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma. Sci Adv. 2023 Dec 15;9(50):eadh9069. doi: 10.1126/sciadv.adh9069. Epub 2023 Dec 13. PMID: 38091397; PMCID: PMC10848745.
  3. Kudo H, Ishida N, Nobukuni T, Aoki Y, Saito S, Nishijima I, Terakawa T, Yamamoto M, Minegishi N, Yamashita R, Kumada K. Detection and Correction of Sample Misidentifications in a Biobank Using the MassARRAY System and Genomic Information. Biopreserv Biobank. 2023 Dec 11. doi: 10.1089/bio.2022.0211. Epub ahead of print. PMID: 38079195.
  4. Kajiwara T, Nishina T, Yamashita R, Nakamura Y, Shiozawa M, Yuki S, Taniguchi H, Hara H, Ohta T, Esaki T, Shinozaki E, Takashima A, Yamamoto Y, Yamazaki K, Yoshino T, Hyodo I. Sidedness-Dependent Prognostic Impact of Gene Alterations in Metastatic Colorectal Cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN). Cancers (Basel). 2023 Oct 27;15(21):5172. doi: 10.3390/cancers15215172. PMID: 37958346; PMCID: PMC10647889.
  5. Du J, Kageyama SI, Yamashita R, Tanaka K, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Hamaya Y, Kojima M, Nakamura Y, Suzuki A, Suzuki Y, Tsuchihara K, Akimoto T. Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I- mediated virus-sensing pathways. Commun Biol. 2023 Aug 5;6(1):818. doi: 10.1038/s42003-023-05080-x. PMID: 37543704; PMCID: PMC10404237.
  6. Nakamura Y, Yamashita R, Okamoto W, Komatsu Y, Yuki S, Ueno M, Kato K, Taniguchi H, Kagawa Y, Denda T, Hara H, Esaki T, Moriwaki T, Sunakawa Y, Oki E, Nagashima F, Nishina T, Satoh T, Kawakami H, Yamaguchi K, Ohtsubo K, Kato T, Horita Y, Tsuji A, Yasui H, Goto M, Hamamoto Y, Wakabayashi M, Ikeno T, Shitara K, Bando H, Tsuchihara K, Miki I, Ichiki H, Ohtsu A, Yoshino T. Efficacy of Targeted Trials and Signaling Pathway Landscape in Advanced Gastrointestinal Cancers From SCRUM-Japan GI-SCREEN: A Nationwide Genomic Profiling Program. JCO Precis Oncol. 2023 Mar;7:e2200653. doi: 10.1200/PO.22.00653. PMID: 36996376; PMCID: PMC10309536.
  7. Tanaka Y, Yamashita R, Kawashima J, Mori H, Kurokawa K, Fukuda S, Gotoh Y, Nakamura K, Hayashi T, Kasahara Y, Sato Y, Fukudo S. Further notice of omics profiles of fecal and oral microbiota change in irritable bowel syndrome patients with diarrhea and symptom exacerbation. J Gastroenterol. 2023 Apr;58(4):427-428. doi: 10.1007/s00535-022-01951-y. Epub 2023 Feb 7. PMID: 36749386.
  8. Hamaya Y, Suzuki A, Suzuki Y, Tsuchihara K, Yamashita R. Classification and characterization of alternative promoters in 26 lung adenocarcinoma cell lines. Jpn J Clin Oncol. 2023 Jan 28;53(2):97-104. doi: 10.1093/jjco/hyac175. PMID: 36465011; PMCID: PMC9885743.
  9. Terui H, Yamasaki K, Wada-Irimada M, Onodera-Amagai M, Hatchome N, Mizuashi M, Yamashita R, Kawabe T, Ishii N, Abe T, Asano Y, Aiba S. <i>Staphylococcus aureus</i> skin colonization promotes SLE-like autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis. Sci Immunol. 2022 Oct 28;7(76):eabm9811. doi: 10.1126/sciimmunol.abm9811. Epub 2022 Oct 28. PMID: 36306369.
  10. Sakai SA, Aoshima M, Sawada K, Horasawa S, Yoshikawa A, Fujisawa T, Kadowaki S, Denda T, Matsuhashi N, Yasui H, Goto M, Yamazaki K, Komatsu Y, Nakanishi R, Nakamura Y, Bando H, Hamaya Y, Kageyama SI, Yoshino T, Tsuchihara K, Yamashita R. Fecal microbiota in patients with a stoma decreases anaerobic bacteria and alters taxonomic and functional diversities. Front Cell Infect Microbiol. 2022 Sep 14;12:925444. doi: 10.3389/fcimb.2022.925444. PMID: 36189350; PMCID: PMC9515963.
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