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 sensing1. 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 processes2, 3

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 sets2, 4-6.   

We are also interested in applying our findings to treat diseases such as cancer, neurodegenerative diseases, and viral infections2


1. Prange-Barczynska et al., bioRxiv, 2023
2. Sugimoto and Ratcliffe, Nature Structural & Molecular Biology, 2022
3. Cockman et al.Proceedings of the National Academy of Sciences, 2022
4. Sugimoto et al.Genome Biology, 2012
5. Sugimoto et al.Nature, 2015
6. Sugimoto et al.Nature Protocols, 2017



Principal investigator

Yoichiro Sugimoto

Work Experience

  • Max Delbrück Center for Molecular Medicine, Germany | Group Leader (2022 - Present) 
  • The Francis Crick Institute, the United Kingdom | Postdoctoral Training Fellow (2016 - 2022) 
    Supervisor: Professor Sir Peter J. Ratcliffe
  • University College London, the United Kingdom | Research Associate (2016-2016)
    Supervisor: Professor Jernej Ule
  • Boston Consulting Group, Japan (2014-2016)


  • University of Cambridge | Ph.D (2010-2014)
    Supervisor: Professor Jernej Ule
  • The University of Tokyo | Master of Integrated Biosciences (2008-2010)
    Supervisor: Professor Yoshikazu Nakamura
  • The University of Tokyo | Bachelor of Engineering (2004-2008)
    Supervisor: Professor Teruyuki Nagamune


Arne Praznik


PhD student

Maike Gräff


Graduate and Undergraduate

Ann-Kathrin Wolf


Research staff

Katrin Räbel



David Schwab


We seek to understand the molecular basis of oxygen sensing. For this, we are investigating dynamic cellular responses that enable us to rapidly adapt to changes in oxygen availability. We are particularly interested in understanding the mechanisms of physiological responses to a decreased oxygen, such as the constriction of blood vessels and the control of breathing. Since dysregulations of oxygen sensing have been observed in a wide-variety of diseases and associated with aging, we believe our research has a great potential for clinical applications. Currently we are focusing on the following research areas.

Oxygen-dependent regulation of mRNA translation

Translational efficiency of mRNA is a key determinant of the expression level of genes. Hypoxia (a decreased oxygen availability) dynamically affects translational efficiency in a global and gene specific manner. Yet, how oxygen availability is transduced to the translational efficiency of mRNA remain to be understood. We have provided key insights on this (Sugimoto and Ratcliffe, Nat Struct Mol Biol., 2022), and working to pinpoint the exact mechanisms.

Oxygen-dependent regulation of phase-separated condensates

Recent studies have underscored a crucial role of molecular condensates in the regulation of gene expression and the cell metabolism. The condensates are typically formed by protein-RNA interactions and work as a compartment in the cell, similar to organelles. We are investigating the molecular mechanisms by which the cell dynamically forms/dissolves molecular condensates upon changes in oxygen availability (Cockman et al., PNAS, 2022).

New technologies

We are tackling fundamental and challenging biological questions. To this end, we have developed numerous new technologies that shed light on a new aspect of biological systems. The new technologies from us include:

  • HP5 (to comprehensively and quantitatively study mRNA translation) (Sugimoto and Ratcliffe, Nat Struct Mol Biol., 2022)
  • hiCLIP (to comprehensively study RNA-RNA interactions recognised by an RNA binding protein in the cell) (Sugimoto et al, Nature, 2015)
  • Computational tools
    • Quantitative analysis of protein modifications using proteomics (Cockman et al., PNAS, 2022)
    • Nucleotide-resolution identifications of protein-binding sites of RNA using CLIP-Seq and iCLIP (Sugimoto et al., Genome Biol. 2012)

We are also currently working on the following technologies:
We are investigating how oxygen availability affects different compartments of the cell using high-resolution/high-throughput imaging analysis.

Induced pluripotent stem cell (iPSC)
In order to understand the oxygen sensing mechanisms in highly oxygen sensitive tissues, we are employing iPSC models.


Hif-2α programmes oxygen chemosensitivity in chromaffin cells
Maria Prange-Barczynska*, Holly Jones*, Yoichiro Sugimoto*, Xiaotong Cheng, Joanna Lima, Indrika Ratnayaka, Gillian Douglas, Keith Buckler, Peter Ratcliffe, Tom Keeley, Tammie Bishop
bioRxiv, 2023 | * co-first

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