Keio University · 생화학·유전·분자생물학
카이베 요시아키 교수의 연구실은 주로 세밀한 세포 신호 전달 메커니즘과 액체 생검(liquid biopsy) 기반 진단 기술을 융합한 연구를 수행하고 있습니다. 특히 NF-κB 및 MBF1 같은 전사 인자와의 상호작용, 과산화물 산화환원 조절, 그리고 장내 미생물 대사산물이 면역 반응에 미치는 영향을 중심으로 면역 조절 메커니즘을 규명하고 있습니다. 또한, 암 진단을 위한 외소체 및 당단쇄 프로파일 분석을 기반으로 한 고감도 진단 기술인 ExoCounter 시스템을 개발하여, 췌장암과 같은 치명적인 암의 조기 진단에 기여하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Reduction/oxidation (redox) regulation mediates numerous cellular responses and contributes to several physiological diseases. The transcription factor nuclear factor kappaB (NF-kappaB) is known to be a redox-sensitive factor. NF-kappaB plays a central role in immune responses and inflammation, through regulation of the gene expression of a large number of cytokines and other immune response genes. NF-kappaB is trapped in the cytoplasm in stimulated cells and translocates into the nucleus in res
Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription factor TATA element-binding protein and gene-specific activators such as the Drosophila nuclear receptor FTZ-F1 or the yeast basic leucine zipper protein GCN4. The human homolog of MBF1 (hMBF1) has been identified but its function, especially in transcription, remains unclear. Here we report the cDNA cloning and functional analysis of hMBF1. Two isoforms,
Osteoclast differentiation factor (ODF)/receptor activator of NF-kappaB ligand is essential for inducing the differentiation of mature osteoclasts. We find that nuclear factor Y (NF-Y) binds to the CCAAT box on the ODF promoter and regulates its basal transcriptional activity. The CCAAT box on the ODF gene is required for its transcriptional induction by vitamin D3, suggesting that NF-Y coregulates this promoter along with VDR. Chromatin immunoprecipitation analysis reveals that NF-Y is required
The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.
Short-chain fatty acids (SCFAs) produced by gastrointestinal microbiota regulate immune responses, but host molecular mechanisms remain unknown. Unbiased screening using SCFA-conjugated affinity nanobeads identified apoptosis-associated speck-like protein (ASC), an adaptor protein of inflammasome complex, as a noncanonical SCFA receptor besides GPRs. SCFAs promoted inflammasome activation in macrophages by binding to its ASC PYRIN domain. Activated inflammasome suppressed survival of Salmonella
Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using
Nanomaterials have extensive applications in the life sciences and in clinical diagnosis. We have developed magnetic nanoparticles with high dispersibility and extremely low nonspecific binding to biomolecules and have demonstrated their application in chemical biology (e.g., for the screening of drug receptor proteins). Recently, the excellent properties of nanobeads have made possible the development of novel rapid immunoassay systems and high-precision technologies for exosome detection. For
Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, speci
Heme (Fe-protoporphyrin IX), an endogenous porphyrin derivative, is an essential molecule in living aerobic organisms and plays a role in a variety of physiological processes such as oxygen transport, respiration, and signal transduction. For the biosynthesis of heme or the mitochondrial heme proteins, heme or its biosynthetic precursor porphyrin must be transported into mitochondria from cytosol. The mechanism of porphyrin accumulation in the mitochondrial inner membrane is unclear. In the pres
Progesterone receptor membrane associated component 1 is a multifunctional heme-binding protein that plays a role in several biological processes such as tumor progression, metabolic regulation, and viability control of nerve cells. Notably, progesterone receptor membrane associated component 1 is highly expressed in various types of cancer cells, and facilitates cancer proliferation and chemoresistance. Recently, progesterone receptor membrane associated component 1 structure has been explored