The University of Tokyo · Medicine
Professor Tatsuhiro Shibata's research lab focuses on the molecular mechanisms underlying gastrointestinal cancers, particularly cholangiocarcinoma and esophageal squamous cell carcinoma. The lab integrates multi-omics approaches—genomics, epigenomics, and transcriptomics—to identify driver mutations, signaling alterations, and therapeutic vulnerabilities in these malignancies. Key research directions include the role of NRF2 pathway activation in therapy resistance, FGFR2 fusions as therapeutic targets in cholangiocarcinoma, and the impact of environmental carcinogens such as liver flukes on tumorigenesis. The lab aims to translate molecular insights into precision oncology strategies, including targeted therapies and novel biomarkers for patient stratification.
Figures are computed from collected data and may differ slightly.
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in <i>ERBB2</i> amplifications and <i>TP53</i> mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy
The nuclear factor E2-related factor 2 (Nrf2) is a master transcriptional activator of genes encoding numerous cytoprotective enzymes that are induced in response to environmental and endogenously derived oxidative/electrophilic agents. Under normal, nonstressed circumstances, low cellular concentrations of Nrf2 are maintained by proteasomal degradation through a Keap1-Cul3-Roc1-dependent mechanism. A model for Nrf2 activation has been proposed in which two amino-terminal motifs, DLG and ETGE, p
FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease.
Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that N
Open papers in the app to read, cite, and organize with AI.
