The University of Tokyo · 의학
Tatsuhiro Shibata 교수의 연구실은 간내세포암과 담도암을 중심으로 한 간장기 암의 분자 기반 메커니즘을 규명하고 있습니다. 특히, 유전적 변이, 에피제네틱 변화, 그리고 전사적 프로파일을 통합 분석하여 암의 이질성과 치료 반응성을 해석합니다. FGFR2 유전자 융합, NRF2 활성화 돌연변이, TP53 및 IDH1/2 변이 등 암의 분자적 특성과 표적 치료 전략의 연관성을 연구하고 있습니다. 이는 새로운 분류 체계와 개인 맞춤형 치료 전략 개발로 이어지는 핵심 연구입니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
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
