Dr Shin-Ichiro Hiraga

External Memberships

Member of the following learned societies:

Biochemical Society; Genetics Society; Molecular Biology Society of Japan

Editorial board member of:

DNA

Ad hoc reviewer for international research journals:

Current Opinion in Cell Biology; Cytogenetic and Genome Research; eLife;  The Journal of Biochemistry; Journal of Cell Science; Nucleic Acids Research; PLoS One 

Research Overview

My research goal is to investigate the mechanisms of chromosome maintenance, particularly those involved in the accurate and robust replication of chromosomal DNA.

My research involves yeast and human cell lines, and I identified Rif1-mediated Protein Phosphatase 1 (PP1) targeting to replication initiation proteins. I showed that RIF1-PP1 controls the initiation of DNA replication by modulating the phosphorylation status of MCM proteins in yeast. (Hiraga et al. 2014 Genes & Development 28: 372-383) and human cells (Hiraga et al. 2017 EMBO Reports 18: 403-419).

Our group is researching Rif1 protein's protective role in DNA replication stress on chromosomes. (Hiraga et al. 2018 EMBO Reports 19: e46222; Garzon et al. 2019 Cell Reports 27: 2558-2566; Watts et al. eLife 2020;9:e58020). These projects aim to expand our knowledge of the mechanisms that maintain integrity in human cells and develop novel approaches to cancer prevention and treatment.

We recently found that SAF-A (also known as HNRNPU) ensures robust DNA replication in human cells by regulating 3D chromatin structure as an RNA-binding and chromatin-associated protein. (Connolly et al. J Cell Sci (2022) 135 (2): jcs258991).

We are using both baker's yeast and cultured human cells as model organisms. Despite their differences in size, shape, and behavior, these cells share many fundamental mechanisms. Surprisingly, many of the genes and proteins found in our cells also exist and play similar roles in tiny yeast cells. These organisms have both advantages and drawbacks as model organisms and complement each other. I aim to combine their strengths to perform good research.

Current Research

I am currently investigating the function of yeast and human RIF1 protein in;

• DNA replication
• Cellular response to replication stress
• Cell proliferation
• Protection of chromosomes from damage during DNA replication stress

I'm also investigating the function of human SAF-A protein in;

• Promoting replication origin licensing
• Assisting replication fork movement
• Promoting cell proliferation

I'm using both classical genetics and cutting-edge technologies such as ;

• Genetic engineering
• Flow cytometry
• Genomics
• Proteomics
• Genome-wide ChIP
• Single-cell replication timing analysis
• Super-resolution microscopy

Collaborations

I am currently playing an important role in a collaboration involving Prof. Anne Donaldson (University of Aberdeen), Dr Tony Ly and Prof. Angus Lamond (University of Dundee), Dr Simon Boulton (Crick Institute) and Prof Jon Higgins (University of New Castle).  I am also conducting international collaboration with Prof Peter Adams (Sanford Burnham Prebys), Dr Ichiro Hiratani (RIKEN Center for Biosystems Dynamics Research, Japan), Dr Masato Kanemaki (National Institute of Genetics, Japan), Professor Chikashi Obuse (Osaka University, Japan) and Professor Katsuhiko Shirahige (University of Tokyo, Japan).

Funding and Grants

Daiwa Anglo-Japanese Foundation Small Grant 2019

Cancer Research UK Programme Award (£1,561,000) ‘How does Rif1 regulate DNA replication and cell recovery after chemotherapeutic replication inhibition?' Grant to Prof Anne Donaldson & Dr Shin-ichiro Hiraga

Friends of ANCHOR Pilot Research Funding 2022 'How Cancer cells multiply and frow: the role of SAF_A variant proteins in cell proliferation in cancer'