ProfessorMark Gorrell

Professor Mark D. Gorrell is devoted to understanding the functions of the dipeptidyl peptidase IV [DPP4] gene family enzymes and the molecular basis of chronic liver disease, including cancer, and how to exploit this knowledge to alleviate human illness. DPP4 is the target of a successful new type 2 diabetes therapy that is benefiting millions of patients.

With colleagues, he discovered that DPP4 modifies the activities of several chemokines [1997 J Exp Med]. He discovered DPP8, DPP9 and DPP10 (2000 FEBS J; 2004 BBA; 2006 BBA) allowing the development of DPP4 selective inhibitors for diabetes therapy, and FAP inhibitors for tumour imaging. His work on DPP4 and DPP9 provided key insights into the safety of DPP4 inhibitors in clinical use [Scand J Immunol; PlosOne]. He also discovered novel substrate recognition sites in DPPs used in drug development, ligand binding sites on DPP4 that are binding sites of MERS virus, and constructed the first DPP4 protein structure prediction [1999 FEBS J; FEBS Lett].

His team showed that DPP4, FAP and DPP9 amplify cell death signals and alter cell adhesion [FEBS J; Hepatology; Mol Cancer Res; BBA-MCR], identified several chemokines cut by DPP8, and identified most of the known substrates of FAP [FEBS J; Peptides; 2019 Mol Cell Proteomics] and DPP9 [FEBS J]. He found that the levels of FAP in human blood specifically correspond to the presence of liver fibrosis and developed this into diagnostic blood test.

He found that mice lacking DPP9 die soon after birth and that these mice have metabolism defects [2013 PlosOne; 2016 Expl Cell Res]. He found that DPP9 is not essential for an intact immune system in adult mice [2019 Sci Rep]. Showed that humans are very likely similar [2021 Cancers] and, in a consortium, that severe DPP9 deficiency in humans causes a severe immune deficiency [2022 Science Immunology].

He uses mouse models of fatty liver, liver fibrosis,NASH and liver cancer [2011 J Hepatol; 2018 Sci Rep; 2021 Cancers, 2025 BBA].