研究内容

A big challenge to elucidate cancer evolutionary process

Some cancer cells in heterogeneous cell populations may be drug-resistant. Those cells are possibly associated with disease recurrence and poor prognosis.

Human cancer cells often consist of heterogeneous populations with various mutations. The combination of mutations in cancer cells varies depending on patients and/or each cancer cell. Cancer develops from mutations in some driver genes and accumulates various genetic mutations through cell growth, leading to intratumor heterogeneity. Intratumoral heterogeneity can be an obstacle to accurate diagnosis and efficient treatment. Therefore, using large-scale data and statistical methods, I analyze how this intratumor heterogeneity is formed and how it evolves.


Understanding of gene regulation and disease mechanism using chromosome conformation data

A new mechanism of hereditary spastic cerebral palsy. Reanalysis of various epigenomic data, including chromosome conformation data, suggested that loss of the DMRT3 enhancer region may contribute to the pathogenesis.

As international epigenome projects advance, there is an increasing understanding of the regulation of tissue and stage-specific gene expression. our laboratory aims to identify the new mechanism of diseases by focusing on the relationship between chromosomal conformation and transcriptional control. We are also studying the molecular evolution of these regulatory mechanisms of gene expression.
In particular, it aims to find differences among species in gene expression control mechanisms that can explain phenotypic differences among species.











Phylogenetic analysis of inbred Rat

Advancement of next-generation sequencing (NGS) technology have led to the advent of an era in which biological genomic data can be used in a variety of fields. In evolutionary biology, data from NGS has made possible phylogenetic analysis at the genomic level. Rat has been widely used as a model animal for human diseases for a long time, and detailed phylogenetic analysis is very important for applied studies such as immunological reaction experiments between substrains. Our laboratory aims to estimate the phylogenetic relationships of inbred rats in more detail based on genomic data.


Comprehensive identification of pseudo-exon activation events

Causative mutations for human genetic disorders have mainly been identified in exonic regions that code for amino acid sequences (Fig. 1). Recently, however, it has been reported that mutations in deep intronic regions can also be cause of certain human genetic disorders by creating novel splice sites, leading to pseudo-exon activation (Fig. 2). The pseudo-exon activation has been discovered by chance until now, but in our laboratory, it is possible to perform comprehensive analysis by using our strength in bioinformatics.



Understanding splicing regulation

The regulatory mechanism of exclusive splicing in the dynamin1 gene. Exons 10a and 10b are suggested to be exclusively selected because of antagonism of RNA secondary structure formation (between pink and light blue) and splicing regulators (red circle).

In eukaryotes, one gene usually gives rise to multiple transcripts by alternative splicing. We are studying to elucidate the control mechanisms and the molecular evolutionally processes. Recently, we identified a network of cis-factors involved in the regulation of exon skipping. We are now conducting comparative genomic analysis to elucidate the mechanisms in exclusive splicing. Recently, it is reported that epigenetic regulation is also associated with the splicing mechanisms and we will also examine the mechanism in detail based on that knowledge.


Exploration of disease-related genes

Click here for a larger image (1261px X 725px).
A mutation that results in an amino acid substitution identified by analysis of exome sequencing data. The upper gray vertical bar represents the allele frequency at each site, and the lower gray horizontal bar corresponds to each sequencing read generated by next-generation sequencing. Among the reads, reads that differ from the reference sequence are shown red. The mutations found in the center of this figure are present in about half of the sequences, which indicates heterozygous in this sample.

In our laboratory, we are conducting exome analyses to explore the causes of multiple genetic diseases. The exome analysis has become a powerful approach with the development of next-generation sequencing, and it would lead to dramatic advances in the identification of disease-causing genes. In the future, we hope to contribute to the identification of disease-causing genes using comparative genome analysis. Please contact us if you are interested in the exome analysis.






The promotion of a cooperative research in data-driven analysis

In analysis of genome, epigenome, and transcriptome data from nextgeneration sequencer, we have to deal with a large amount of data utilizingcomputer.Moreover, as genome sequencing in various species is frequently performed,comparative genome analysis is widely conducted. The needs of data analysisare remarkably increasing in molecular life science research. There is no doubtthat this tendency is not transient but permanent, which will be more strongerin the future.Therefore, we are actively promoting a cooperative research to provide newmolecular biological evidence from the utilization of a new method to dataanalysis. Moreover, we are conducting education activity for the promotion ofdata-driven analysis.Please contact us anytime.

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