Pinto-Fernández Group | Translational Ubiquitomics - Cancer Immunology

adan.pintofernandez@ndm.ox.ac.uk

Our lab has an interest in studying how cellular Ubiquitylation and ISGylation influence cancer inflammation 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.

RESEARCH OVERVIEW

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

For instance, we have recently discovered that cancer cells lacking the DUB 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.

Pinto-Fernandez, A., Salio, M., Partridge, T. et al. Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity. Br J Cancer 124, 817–830 (2021). (DOI: 10.1038/s41416-020-01167-y).

Other relevant references:

https://doi.org/10.3389/fgene.2016.00133

https://doi.org/10.3390/biom12020300

DOI: 10.1038/nature24451

https://doi.org/10.7554/eLife.71596

DOI: 10.26508/lsa.202000768

https://doi.org/10.1083/jcb.202004211

DOI: 10.1126/science.ade8840

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, Incyte, Xcellomics, ONO, FORMA therapeutics, and others). This provides an excellent opportunity to learn the complementary research dynamics happening in pharmaceutical companies.

References on methodology:

https://doi.org/10.3390/biom10101453

https://doi.org/10.3390/ijms23063263

https://doi.org/10.3389/fchem.2021.640105

https://doi.org/10.3389/fchem.2019.00592

PREVIOUS MEMBERS

Ms Beyza Akgun (MBiochem; 2022-2023)

Our Team

Adan Pinto Fernandez

Career Development Fellow at Chinese Academy of Medical Sciences Oxford Institute (CAMS) - Nuffield Department of Medicine
Simeon Draganov

Postdoctoral Scientist
Hannah Scott

Research Assistant
Hedib Alrawili

DPhil Student in Clinical Medicine
Haofeng Chen

DPhil Student
Alice Beard

Research Assistant