Sugimoto Lab

Molecular mechanisms of environment sensing


Our laboratory aims to understand how cells sense the environment, such as the availability of oxygen, by developing cutting edge high-throughput experimental and computational techniques.

The human body adapts to varying environments. For this, the cells sense the availability of molecules crucial for their survival, such as oxygen and nutrients. We are particularly interested in the molecular basis of rapid oxygen sensing. Due to the critical importance of oxygen to life, the cell must rapidly respond to the changes in oxygen availability. However, the molecular mechanisms largely remain to be understood. 

Our current focus is to understand the roles of RNA in rapid oxygen sensing. RNA acts as the carrier of the genetic information of a gene, and the information is used to synthesize “the functional product”, protein. However, during its life cycle, RNA dynamically interacts with other molecules and RNA can even form a large compartment through phase separation in the cell. The interaction of RNA and other molecules affects not only the synthesis rate of the encoded protein, but also many other functions of the cells.  We are investigating how the availability of oxygen controls these RNA-mediated processes1, 2

We are developing innovative high-throughput technologies that can comprehensively measure the interactions and regulatory status of key biological molecules (e.g. RNA and protein), and are employing data science to make sense of the complex data sets1, 3-5.   

We are also interested in applying our findings to treat diseases such as cancer, neurodegenerative diseases, and viral infections1

1. Sugimoto and Ratcliffe, Nature Structural & Molecular Biology, 2022
2. Cockman, Sugimoto et al.Proceedings of the National Academy of Sciences 2022

3. Sugimoto et al., Genome Biology, 2012
4. Sugimoto et al., Nature, 2015
5. Sugimoto et al., Nature Protocols, 2017


Isoform-resolved mRNA profiling of ribosome load defines interplay of HIF and mTOR dysregulation in kidney cancer
Yoichiro Sugimoto, and Peter J. Ratcliffe
Nature Structural & Molecular Biology 2022

Widespread hydroxylation of unstructured lysine-rich protein domains by JMJD6
Matthew E. Cockman, Yoichiro Sugimoto, Hamish B. Pegg, Norma Masson, Eidarus Salah, Anthony Tumber, Helen R. Flynn, Joanna M. Kirkpatrick, Christopher J. Schofield, and Peter J. Ratcliffe
Proceedings of the National Academy of Sciences 2022

USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer
Jessica K. Nelson, May Zaw Thin, Theodore Evan, Steven Howell, Mary Wu, Bruna Almeida, Nathalie Legrave, Duco S. Koenis, Gabriela Koifman, Yoichiro Sugimoto, Miriam Llorian Sopena, James MacRae, Emma Nye, Michael Howell, Ambrosius P. Snijders, Andreas Prachalias, Yoh Zen, Debashis Sarker, and Axel Behrens
Nature Communications 2022

Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein
Yoichiro Sugimoto, Anob M. Chakrabarti, Nicholas M. Luscombe, and Jernej Ule
Nature Protocols 2017

A retained intron in the 3′‐ UTR of Calm3 mRNA mediates its Staufen2‐ and activity‐dependent localization to neuronal dendrites
Tejaswini Sharangdhar, Yoichiro Sugimoto, Jacqueline Heraud‐Farlow, Sandra M Fernández‐Moya, Janina Ehses, Igor Ruiz Mozos, Jernej Ule, and Michael A Kiebler
EMBO reports 2017

hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1
Yoichiro Sugimoto, Alessandra Vigilante, Elodie Darbo, Alexandra Zirra, Cristina Militti, Andrea D’Ambrogio, Nicholas M Luscombe, and Jernej Ule
Nature 2015

iCLIP: Protein–RNA interactions at nucleotide resolution
Ina Huppertz, Jan Attig, Andrea D’Ambrogio, Laura E Easton, Christopher R Sibley, Yoichiro Sugimoto, Mojca Tajnik, Julian König, and Jernej Ule
Methods 2014

Structure of the large ribosomal subunit from human mitochondria
Alan Brown, Alexey Amunts, Xiao Chen Bai, Yoichiro Sugimoto, Patricia C. Edwards, Garib Murshudov, Sjors H.W. Scheres, and V. Ramakrishnan
Science 2014

NSun2-Mediated Cytosine-5 Methylation of Vault Noncoding RNA Determines Its Processing into Regulatory Small RNAs
Shobbir Hussain, Abdulrahim A. Sajini, Sandra Blanco, Sabine Dietmann, Patrick Lombard, Yoichiro Sugimoto, Maike Paramor, Joseph G. Gleeson, Duncan T. Odom, Jernej Ule, and Michaela Frye
Cell Reports 2013

Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain
Boris Rogelj, Laura E. Easton, Gireesh K. Bogu, Lawrence W. Stanton, Gregor Rot, Tomaž Curk, Blaž Zupan, Yoichiro Sugimoto, Miha Modic, Nejc Haberman, James Tollervey, Ritsuko Fujii, Toru Takumi, Christopher E. Shaw, and Jernej Ule
Scientific Reports 2012

Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions
Yoichiro Sugimoto, Julian König, Shobbir Hussain, Blaž Zupan, Tomaž Curk, Michaela Frye, and Jernej Ule
Genome biology 2012

Poly(ethylene glycol)-lipid-conjugated antibodies enhance dendritic cell phagocytosis of apoptotic cancer cells
Urara Tomita, Satoshi Yamaguchi, Yoichiro Sugimoto, Satoshi Takamori, and Teruyuki Nagamune
Pharmaceuticals 2012