Professor TAKAHASHI Chiaki
Faculty, Affiliation
Cancer Research Institute
College and School Educational Field
Division of Medical Sciences, Graduate School of Medical Science
Division of Natural Sciences, Graduate School of Natural Science and Technology
Division of Medicine, Graduate School of Medical Science
Division of Natural System, Graduate School of Natural Science and Technology
Course in Biosystems, School of Biological Science and Technology, College of Science and Engineering
School of Medicine, College of Medical, Pharmaceutical and Health Sciences
Laboratory
Division of Oncology and Molecular Biology TEL:076-246-6750 FAX:076-234-4521
Academic Background
【Academic background(Doctoral/Master's Degree)】
Kyoto University Doctor Graduate School, Division of Medicine 199603 Completed
【Academic background(Bachelor's Degree)】
Kyoto University 199003
【Degree】
MD., Ph. D.,
Career
Professor(2009/12/01-)
Associate Professor(2004/01/01-2008/03/31)
Assistant Professor(1996/06/01-2003/12/01)
Year & Month of Birth
1964/10
Academic Society
Japan Cancer Association
Award
○JFCR Young Investigators Award(2004/10)
Specialities
Pathological medical chemistry
Speciality Keywords
Cancer Genetics,Molecular Biology,Molecular Oncology
Research Themes
Molecular mechanism of tumorigenesis, progression, metastasis and cancer stem cells
We inquire the minimum requirement for inducing tumor progression and cancer stem cells. We also investigate the genetic interactions between such minimum requirements. We plan to establish in vitro cancer stem cell models that stably express various features cancer stem cells on dish. Such system would critically contribute to screen genes related to cancer stem cells or to develop drugs specifically targeting cancer stem cells.
Tumor suppressor function of RECK
We isolated RECK gene as an antagonistic downstream target of K-rasV12. It encodes a GPI-anchored glycoprotein with multiple domains analogous to EGF, crmA and metalloendopeptidase substrates. RECK regulates Ras, beta1-integrin and Notch signaling through interaction with several soluble MMPs, MT1-MMP, ADAM10 and CD13/APN. RECK expression in various cancers significantly predicts favorable prognosis of patients. Many scientists are interested in transcriptional/post-transcriptional regulation of this gene by various oncogenic signals. We particularly focus on the cellular signals controlled by RECK.
Analysis of Rb-Ras pathway
We focus on the genetic interaction of Rb and Ras in mammals. Ras regulates phosphorylation status of Rb via D-type Cyclins and CDK4/6; inversely, Rb controls isoprenylation of Ras in E2F- and SREBP-dependent manner. We found Rb-deficient carcinogenesis in thyroid C cells is antagonized by elevated N-Ras activity and subsequent DNA damage response and cellular senescence. We speculate that this Rb-Ras interaction plays critical roles in developing cancer stem cells. We are testing this hypothesis using various compound knockout mice.
tumor metabolism, microenvironment
Books
Papers
- ATM mediates pRB function to control DNMT1 protein stability and DNA methylation. Shamma A, Suzuki M, Hayashi, N, Kobayashi M, Sasaki N, Nishiuchi T, Doki Y, Okamoto T, Kohno S, Muranaka H, Kitajima S, Yamamoto K, Takahashi C MOLECULAR AND CELLULAR BIOLOGY 13 10 2013/06
- Twists in views on RB functions in cellular signaling, metabolism and stem cells. 103 1105-1116 2012/01
- Rb/E2F1 regulates the innate immune receptor Toll-like receptor 3 in epithelial cells. MOLECULAR AND CELLULAR BIOLOGY 2012/01
- Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling. Shunsuke Kitajama, Chiaki Takahashi et al., ONCOGENE 30 6 737-750 2011/02
- The beta1-integrin-dependent function of RECK in physiologic and tumor angiogenesis. Miki T, Shamma A, Kitajima S, Takegami Y, Noda M, Nakashima Y, Watanabe K, Takahashi C. Mol Cancer Res. 8 5 665-676 2010/04
- Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Shamma A, Takegami Y, Miki T, Kitajima S, Noda M, Obara T, Okamoto T, Takahashi C. Cancer Cell 15 4 255-269 2009/04
- RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity. Muraguchi T, Takegami Y, Ohtsuka T, Kitajima S, Chandana EP, Omura A, Miki T, Takahashi R, Matsumoto N, Ludwig A, Noda M, Takahashi C. Nature Neuroscience 10 7 838-845 2007/07
- The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interacts with membrane type 1 matrix metalloproteinase and CD13/aminopeptidase N and modulates their endocytic pathways. J. Biol. Chem. 282 16 12341-12352 2007/04
- Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Takahashi C, Contreras B, Iwanaga T, Takegami Y, Bakker A, Bronson RT, Noda M, Loda M, Hunt JL, Ewen ME. Nature Genetics 38 1 118-123 2006/01
- J Biochem. 2013 Aug 5. [Epub ahead of print] Regulatory interaction between NBS1 and DNMT1 responding to DNA damage. Hayashi N, Kobayashi M, Shamma A, Morimura Y, Takahashi C, Yamamoto KI.
Conference Presentations
Others
Arts and Fieldwork
Patent
Theme to the desired joint research
○Development of drugs targeting cancer stem cells and cancer cell metabolism.
Grant-in-Aid for Scientific Research
○「Rbがん抑制遺伝子欠失によって誘導される蛋白質高イソプレニル化の研究」(2009-2011)
Competitive research funding,Contribution
Collaborative research,Consignment study
Classes (Bachelors)
Classes (Graduate Schools)
○Oncology and Molecular Biology(2017)
○Oncology and Molecular Biology(2017)
○Molecular Oncology(2017)
○Medical Sciences(2017)
○Medical Sciences(2017)
○Cancer molecular pathology 2(2017)
○Cancer molecular pathology 2(2017)
○Oncology and Molecular Biology(2017)
○Cancer molecular pathology 2(2017)
○Biology of Cancer 2B(2017)
○Biology of Cancer 2A(2017)
○Cancer molecular pathology 2(2017)
○Oncology and Molecular Biology(2016)
○Molecular Oncology(2016)
○Oncology and Molecular Biology(2016)
○Oncology and Molecular Biology(2016)
○Biology of Cancer 2B(2016)
○Biology of Cancer 2A(2016)
○Cancer molecular pathology 2(2016)