Pharmacogenetic and proteomic characterisation of response to Dipeptidyl peptidase-1 inhibitors: precision medicine for a novel class of anti-inflammatory drugs

Dipeptidyl peptidase-1 (DPP1) inhibitors are a novel class of immunomodulatory drug which have recently shown positive results in a phase 3 clinical trial in people with the chronic inflammatory lung disease bronchiectasis and are in development for a number of other inflammatory conditions including hidradenitis suppurativa and chronic rhinosinusitis.

DPP1 inhibitors target neutrophils, and particularly the neutrophil serine proteases elastase, cathepsin G and proteinase-3, responsible for tissue damage and perpetuating pro-inflammatory responses, and so may be a potential treatment for a number of neutrophil-driven inflammatory diseases.

Trials in bronchiectasis show important differences between patient groups in their response to DPP1 inhibitors. This suggests that an individual’s response to these drugs may be affected by differences in genetics (pharmacogenetics- differences in drug targets or metabolism of drugs between populations).

This project will combine a clinical translational study, investigating the proteome and transcriptome of neutrophils from different patient populations, and analysis of unique datasets (large population genetic datasets) and data taken from clinical trials of DPP1 inhibitors to investigate differences between patient groups in the neutrophil proteome, neutrophil functional responses, the genetics of DPP1 and its target proteases and how this translates into different responses to DPP1 inhibitors. Full training will be provided in bioinformatic and wet lab techniques.

The project will be most suited to a candidate keen to pursue a career in immunology, pharmacology and translational research involving patients.

The Respiratory research group at the University of Dundee is a world leading centre for translational research into inflammation and infection in respiratory disease. Previous PhD students have won multiple awards and students regularly published in high impact journals.

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Fully funded by the European Respiratory Society through the EMBARC project (European Bronchiectasis Network).

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