COI-The Wellcome Centre for Human Genetics and NDM Research Building, Old Road Campus
Career Development Fellow at Chinese Academy of Medical Sciences Oxford Institute (CAMS) - Nuffield Department of Medicine
TRANSLATIONAL STUDIES OF THE UBIQUITIN SYSTEM - CANCER IMMUNOLOGY
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). https://doi.org/10.1038/s41416-020-01167-y
Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6
Dietz L. et al, (2023), Science, 379, 1112 - 1117
Structural Premise of Selective Deubiquitinase USP30 Inhibition by Small-Molecule Benzosulfonamides
O’Brien DP. et al, (2022)
Structural basis for antagonism of the ubiquitin ligase BIRC6 by SMAC
Dietz L. et al, (2022)
Comprehensive Landscape of Active Deubiquitinating Enzymes Profiled by Advanced Chemoproteomics
Pinto-Fernández A. et al, (2019), Frontiers in Chemistry, 7
Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting
Olie CS. et al, (2019), iScience, 12, 318 - 332