Laboratory for Cellular Epigenomics

Research Topics

 

Development of a novel epigenome technology

Although many excellent technologies have been developed in recent years to study epigenome, there are still technological walls in the field that are limiting us to understand the very complex cellular regulatory system. Histone modifications are incredibly complex, as there are over 300 different histone modifications reported to date, which are found in different combinations in the nucleosome to regulate transcription. Currently available epigenomic technologies limit us to study one at a time in most cases. One of our missions is to develop a next generation epigenomic platform to enable studying genomic locations of multiple histone modifications simultaneously.

 

Studying epigenomes of Osteoarthritis

Epigenomic studies have not been carried out very much with the clinical samples for studying diseases, since conventional protocols have required a large number cells that are typically not available with the clinical samples. However, it is critically important that we study them directly rather than cell lines, for example, which most like do not retain all the pathogenesis elements. Osteoarthritis (OA) is a common joint disorder of thinning cartilage that becomes increasingly more common with age. It is a large and growing global health burden that represents one of the most common causes of chronic disabilities in the Western world. There is no effective cure except for joint replacement surgery. We have recently applied ATAC-seq (Assay for Transposase Accessible Chromatin with high-throughput sequencing) on OA patient samples. ATAC-seq determines open chromatin regions, mainly enhancer regions, and since it requires far fewer cells than conventional epigenomic protocols, we could successfully apply it on clinical hard tissue samples. Integrative analysis of ATAC-seq data with publicly available datasets such as the GWAS, DNA methylation and RNA-seq have revealed potential pathways that may be contributing towards it pathogenesis.



PubMed: Chromatin accessibility landscape of articular knee cartilage reveals aberrant enhancer regulation in osteoarthritis.

 

Ageing Data Resource

How chromatin changes as we age appear to be different from tissue to tissue, from cell type to cell type. Comprehensive approach has not been taken to date to understand how the chromatin and the subsequent processes change as aging progresses, and thus, one of our goals is to generate multiple omics datasets (such as epigenome, transcriptome and metabolome) on selected mouse tissues, and carry out integrative analyses. Furthermore, importance of the gut microbiome is becoming more and more evident, and how it may contribute to ageing is currently unknown, which we aim to also get an insight into. By employing single cell transcriptome, we also aim to determine how cell type landscape changes for each tissue over ageing.