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Laboratory of Genome Technology
Team Katagiri Member & Research Interests

Member (As of Apr, 2007)

Toyomasa Katagiri, Ph. D.

Meng-Lay Lin, Ph. D.

Jae-Hyun Park, MSc

Sachiko Dobashi, MSc

Masahiko Ajiro, MSc

Jung-won Kim, MSc

Chikako Fukukawa, Ph. D.

Tomomi Ueki, M. D., Ph. D.

Yosuke Harada, Ph. D.

Jun Fujiwara, M. D.

Akira Togashi, MSc

Ms. Kyoko Kijima

Ms. Kie Naito

Ms. Yoshiko Fujisawa

Ms. Akiko Konuma

Ms. Aya Sasaki


Research Interests

The determination of human genome sequence has been completed as a result of human genome project. Thus, it is now crucial to clarify the function of genes in the genome. Particularly functional analysis of genes associated with human diseases is a matter of great importance. Microarray that enables to detect expression of thousands of genes with an experiment is a powerful tool for the research of carcinogenesis in terms of basic research as well as clinical research.
We fabricated our in-house microarray slides containing 32,256 genes that correspond almost of all genes in the human genome. We have been performed expression profile analyses in a breast cancers, renal cell carcinomas, bladder cancers and soft tissue tumors using the cDNA microarray in combination with LMM (Laser Microbeam Microdissection). To obtain the precise expression profile of human cancers, we selectively collected cancer cells by LMM from clinical tissues that are a mixture of cancer cells, stromal cells, endothelial cells, and infiltrating lymphocytes (Fig. 1).
We also analyzed expression profiles of 30 normal human tissues. Through these microarray data, we have identified several candidate genes that are overexpressed in cancer cells and not expressed in vital organs, as candidates for novel molecular targets of therapeutic drugs, antibodies, and peptide vaccine and/or diagnosis of human cancers. Particularly, through synovial sarcomas (SS) of soft tissues tumors, we focused on Frizzled homologue 10 (FZD10), a member of Frizzled family, is exclusively up-regulated in SS and its expression is not or hardly detectable in normal organs. Treatment of two SS cell lines with small interfering RNA (siRNA) decreased the protein expression of FZD10 specifically and suppressed their cell growth. Moreover, the specific polyclonal antibody against extracellular domain of FZD10 was markedly effective in mediating antibody-dependent cell cytotoxity (ADCC) against FZD10-overexpressing SS cells in vitro, and also effective in vivo, attenuating the growth of SS xenografts in nude mice. Furthermore, monoclonal antibody (Mab) to FZD10 we established was shown to have specific binding activity against FZD10 on cell lines expressing FZD10. To further validate the specific binding activity of those antibodies in vivo, we injected fluorescent-labeled mAb intraperitoneally or intravenously into the mice carrying SS xenografts and found that this mAb was bound to the FZD10-expressing tumors, but not to any other normal mouse tissues by the use of the in vivo fluorescent imaging system (Fig. 2). Taken together, this specific Mab against FZD10 could be utilized as the novel treatment of SS with minimal or no risk of adverse reactions.

1.Functional analysis of molecular-targets for breast, bladder and kidney cancer therapies

2.Development of prediction system of chemosensitivity to M-VAC neoadjuvant chemotherapy in bladder cancers.

Fig.1

Fig.2

Copyright © 2007 Yusuke Nakamura's Labo., All rights reserved.
Last update: 2007.4.4

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