608-262-1686 (Office) ; 608-262-8008 (Lab)
6533 WI Institute Medical Research
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BA, 2005, Pharmacology, The Kyushu University, Japan
PhD, 2010, Genetics, National Institute of Genetics, Japan
Postdoctoral Research, University of North Carolina at Chapel Hill
Assistant Professor of Oncology
Cancer Genetics & Epigenetic Mechanisms Program Member, UW Carbone Cancer Center
Steering Committee, UW Madison Optical Imaging Core
During cell division, sister chromatids need to be divided equally into two daughter cells to maintain genome stability. In order to achieve accurate chromosome segregation, microtubules must be properly assembled at a specific chromosome site that is called the kinetochore. A kinetochore is a macromolecular protein complex on centromere chromatin. Improper microtubule-kinetochore attachment causes aneuploidy, micronuclei, and numerous developmental diseases including trisomies. These disorders demonstrate how understanding the mechanisms underlying faithful chromosome segregation is important for various fields of study. Aneuploidy is particularly important, as ~90% of solid tumors and ~50% blood tumor show aneuploidy. However, it remains unclear the mechanisms of how cells achieve accurate chromosome segregation, what causes aneuploidy, and how chromosomal instability (including aneuploidy) contributes to carcinogenesis and cancer progression.
Our lab focuses on discovering the molecular mechanisms underlying force production, mitotic checkpoint control, and error correction in accurate cell division, with a focus on the role of the highly conserved Ndc80 complex and the kinetochore structural integirty. We recently developed a FRET (fluorescent resonance energy transfer)-based Ndc80 tension biosensor, which allows us to measure cellular tension using light microscopy. Using this tension biosensor, we will elucidate the mechanisms of how kinetochores generate and transmit force for accurate chromosome segregation. Tension at kinetochores may be important for the kinetochore deformation, which is thought to be critical for mitotic checkpoint control. We will investigate the kinetochore structural changes by super-resolution microscopy, electron microscopy, and ExM (expansion microscopy). In addition, we are committed to understanding how the loss of centromere/kinetochore integrity causes carcinogenesis and cancer progression. We recently found that the CENP-H/I complex, which is a member of core-kinetochore proteins, is overexpressed in primary colon cancer and its expression levels inversely depends on the stage of cancer progression. We are investigating the functions of CENP-H/I complex in cancer. In order to reveal centromere/kinetochore functions, our lab uses advanced light and electron microscopy techniques. They include quantitative confocal microscopy to measure cellular protein copy number, light-sheet microscopy for high spatial/temporal live cell imaging, various super-resolution microscopy (SIM/STORM/STED) for nm-scale analysis, FRET-based tension biosensor, FRAP/TIRF system for cellular protein dynamics, and immuno-electron microscopy.
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