Our laboratory conducts diverse research aimed at elucidating the genetic regulation of immune disease susceptibility. These research findings are expected to reveal pathological conditions directly linked to the risk of developing immune diseases.

I. Functional Genomics

We have conducted functional genomics research to understand the genetic regulation of human immune disease susceptibility (Ishigaki et al. Nat Genet 2017). In recent years, we have further expanded our functional genomics research to include genome editing experiments using CRISPR-Cas9 technology, single-cell eQTL analysis, and multi-omics data analysis.

II. T cell receptor (TCR) 

HLA gene polymorphisms are the most significant risk factors for immune diseases. Recently, we discovered that HLA gene polymorphisms substantially modify the amino acid composition of the complementarity determining region 3 (CDR3), which is the hypervariable region of TCR. Furthermore, we demonstrated that this TCR modification by HLA gene polymorphisms enhances reactivity to pathogenic antigens (such as citrullinated antigens in rheumatoid arthritis) (Ishigaki et al., Nat Genet 2022). In another research project, by developing a new analysis algorithm, we successfully captured the characteristic amino acid patterns of regulatory T cell TCRs (Lagattuta et al., Nat Immunol 2022).

III. Clinical Applications

The Polygenic Risk Score (PRS) is a score that predicts genetic risk at the individual level. Recently, we developed a new analysis algorithm for calculating PRS (Amariuta and Ishigaki et al. Nat Genet 2020). By expanding this research further, we are evaluating the clinical utility of PRS.