The University of Tokyo · 면역·미생물학
마카토 요시기 교수의 연구실은 히스톤 에피제네틱스, 전사체 및 에피트랜스크립토믹스의 변화를 중심으로 HTLV-1에 의한 T세포 백혈병/림프종의 발병 기전을 밝히는 데 초점을 맞추고 있습니다. 특히 H3K27me3 메틸화, m⁶A 변환 등 에피제네틱스 및 에피트랜스크립토믹스의 조절 메커니즘을 규명하며, 암세포의 비정상적 유전자 발현을 정상화하는 새로운 약물 타겟을 모색하고 있습니다. 임상적 적용을 목표로 한 약물 개발과 함께, 전장 유전체, 에피제놈, 전사체 분석을 융합한 종합적 분석을 통해 ATL의 병태생리학적 이해를 심화하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Epigenomes enable the rectification of disordered cancer gene expression, thereby providing new targets for pharmacological interventions. The clinical utility of targeting histone H3 lysine trimethylation (H3K27me3) as an epigenetic hallmark has been demonstrated<sup>1-7</sup>. However, in actual therapeutic settings, the mechanism by which H3K27me3-targeting therapies exert their effects and the response of tumour cells remain unclear. Here we show the potency and mechanisms of action and resi
Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible
Human T-cell Leukemia Virus Type 1 (HTLV-1) is a pathogenic human retrovirus that is responsible for intractable diseases such as adult T-cell leukemia-lymphoma (ATL), a malignancy with a poor patient prognosis. Although recent studies have delineated several genomic, epigenomic, and transcriptomic abnormalities associated with HTLV-1, to date the importance of epitranscriptomic modifications, particularly N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), remains unclear. Here, we showed that the
T-cell lymphomas are clinically and biologically heterogeneous malignancies that comprise ~ 10% of non-Hodgkin lymphomas. Outcomes with first-line chemotherapy remain poor. Over the past decade, integrative genomic and epigenomic studies have defined recurrent abnormalities converging on proximal T-cell antigen receptor/costimulatory signaling to the NF-κB/NFAT, JAK/STAT, PI3K/AKT/mTOR, and NOTCH pathways, alongside pervasive alterations in chromatin modifiers and the DNA methylation machinery.
Adult T-cell leukemia/lymphoma (ATL) is an aggressive and refractory hematologic malignancy that is caused by human T-cell leukemia virus type-1 (HTLV-1) retrovirus. ATL results from a combination of viral latency and the accumulation of abnormalities throughout the genome, epigenome, transcriptome, and signaling pathways. Despite numerous studies, the data have been largely fragmentary, and a comprehensive understanding of this disease remains unclear. Recent comprehensive analyses have contrib
