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Molecular Genetics of Human Diseases


Prof. Kato
ProfessorF Kikuya KATO
 
 
URLF http://genome.mc.pref.osaka.jp/
Overview
  Following recent advances in bioscience, particularly molecular biology, it is becoming possible to directly analyze cancer tissue in individual patients. Our laboratory is aimed at establishing new oncology, making use of not only conventional gene manipulation technology but also techniques of genomic science and bioinformatics. In parallel to these efforts, we are also conducting research on application of basic research outcomes to the bedside practice (so-called translational research).

Research Areas
  1. Analysis of cancer tissue architecture
    Cancer is not an assembly of monoclonal cancer cells but is composed of various subclones involving different somatic mutations. In most cancers, non-cancerous cells are interposed. Depending on the site, environmental factors (oxygen concentration, etc.) vary, indicating limitations in the applicability of the conventional view that entire cancer tissue can be regarded as homogeneous tissue. At our laboratory, several areas of a given cancer tissue are sampled separately for analysis of gene expression and mutation in individual areas, with a goal of clarifying how the entire cancer tissue is formed from individual areas. To put it more concretely, we will investigate how the sensitivity to anti-cancer drugs of the entire cancer tissue is determined by the features of individual subclones, since the sensitivity is naturally expected to differ among different subclones.
  2. Development of methods for diagnosis and treatment making use of gene expression profiles
    Chemotherapy plays an important role in treatment of cancer. However, about half of all patients with cancer fail to respond to chemotherapy. Because anti-cancer agents often induce severe adverse reactions, the stress on patients will be alleviated if their responses to treatment can be predicted in advance. This is called personalized medicine (tailor-made medicine). If gene expression profile analysis, a technique of genomic science, is used, pre-treatment evaluation of patientfs responses may be possible. At present, efforts are being made not only to apply gene expression profiles to prediction of patientfs sensitivity to anti-cancer agents but also to develop methods of diagnosis and treatment making use of gene expression profiles for patients with mammary, hepatic, esophageal, pulmonary, cerebral and other cancers. The outcomes from these studies have been published on Cancer Gene Expression Database (CGED, http://cged.hgc.jp).
  3. Development of gene analysis technology
    We have succeeded for the first time in the world in developing high-throughput quantitative PCR (adaptor-tagged competitive PCR; ATAC-PCR) and have been applying this technique of PCR to cancer expression profile analysis. At present, we are conducting research for application of ATAC-PCR to genomic structure analysis.

References
  1. Iwao-Koizumi K. et al., Journal of Clinical Oncology, 23, 422-431, 2005.
  2. Kato K. et al., Nucleic Acids Res., 25, D533-D536, 2005.
  3. Kato K., Nucleic Acids Res., 33, 4694-4696, 1997.
  4. Kato K., Trends Neurosci., 15, 319-323, 1992.


Fig. 1   Diversity of cancer cells within a tumor



Fig. 2   Personalized medicine (tailor-made medicine)



Fig. 3   Adaptor-tagged competitive PCR (ATAC-PCR)