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Our lab has an interest in studying how cellular Ubiquitylation and ISGylation influence cancer immune evasion with the final aim of translating these findings into valid therapeutic targets. To study these pathways we use state-of-the-art MS-based omics techniques such as proteomics and lipidomics in combination with immunology and cellular biology functional assays.

ISGylation and IFN-I Production and Response Pathways © Biorender
deISGylating Enzymes and IFN-I Signalling

RESEARCH OVERVIEW

Current research involves the study of the roles of a class of druggable enzymes called deISGylating enzymes in cancer immunology using advanced proteomics, lipidomics, and immunology techniques as main tools.  

For instance, we have recently discovered that cancer cells lacking the deISGylating enzyme USP18, a negative regulator of the interferon pathway, are more antigenic and radiosensitive. At a molecular level, USP18-deficient cells accumulate innate immune ligands such as dsRNA, enhance the antigen presentation machinery, and hence they can activate more efficiently cytotoxic T cells, resulting in enhanced T cell killing and immunotherapy responses. In addition, we have recently discovered two new deISGylating enzymes, USP16 and USP24 that we are currently investigating. 

 

TRAINING OPPORTUNITIES

We are experts in the study of the ubiquitin system in disease-relevant models using advanced ubiquitomics (GG-petidomics), activity-based protein profiling (ABPP), proteomics, lipidomics, chemical biology, cellular biology, and immunology techniques. These methodologies and matching data analysis approaches can be applied and learned in our laboratory. Importantly, as part of the COI-NDM environment, we have access to cutting-edge technology assuring the highest available standards in terms of data quality. 

Finally, our laboratory has been always very interested in the translational aspect of our research and as a consequence, we have been involved in a number of collaborations with industry partners, including Pfizer, Boehringer Ingelheim, Incyte, Xcellomics, ONO Pharma, FORMA therapeutics, and others. This provides an excellent opportunity to learn the complementary research dynamics happening in pharmaceutical companies.

PUBLICATIONS

CURRENT TEAM:

Current team members

PREVIOUS MEMBERS

Ms Beyza Akgun (MBiochem; 2022-2023) 

Ms Hannah Claire Scott (Research Assistant; 2018-2025)

Our Team

Collaborators

Vincenzo D'Angiolella - WIMM (Department of Oncology)

Paul Elliot - Department of Biochemistry

Madalena Tarsounas - Department of Oncology

Tim Elliot - CIO (NDM)

Eleni Admaopoulou - CIO (NDM)

Richard Cornall - NDM

Jan Rehwinkel - WIMM (RDM)

Ricardo Fernandes - CAMS-COI (NDM)

Tao Dong - CAMS-COI (NDM)

Benedikt Kessler - CAMS-COI (NDM)

Geoffrey Smith - (Dunn School)

Persephone Borrow - NDM

Darragh O'Brien - CMD/TDI (NDM)

Pablo Cespedes - CAMS-COI (NDM)

Nikolaos Kanellakis - CAMS-COI (NDM)

Yi-Ling Cheng - CAMS-COI (NDM)

Peter Wing - CAMS-COI (NDM)

Roman Fischer - TDI (NDM)

Dan Ebner - TDI (NDM)

Chris Schofield - Chemistry (Oxford)

Lennart Brewitz - Chemistry (Oxford)

FUNDING

Chinese Academy of Medical Sciences Oxford Institute

Boehringer Ingelheim

Ono Pharma

OCION - CRUK

Xcellomics

Related research themes