Peptidylarginine Deiminases and Extracellular Vesicles in Health and Disease
Professor Sigrun Lange leads an internationally pioneering cross-disciplinary research programme in Experimental Pathology and Pathobiology. Focusing on Peptidylarginine deiminases (PADs) and Extracellular Vesicles (EVs), this project elucidates novel mechanisms underpinning evolution of the immune system and fundamental pathobiological and physiological processes.
This work uses in vitro human, in silico and in vivo comparative animal-models across the phylogeny tree, including in species with unusual immune and metabolic features such as resistance to cancer, ageing and hypoxia, as well as various models for neurodegenerative disease, tissue regeneration, and models of host-pathogen interactions and infection. Aims include the discovery of novel mechanisms underlying key concepts in the evolution of immune responses to inform human pathologies, for therapeutic and drug-directed strategies, for disease fingerprinting and biomarker discovery in human and animal health.
Biological Effects of Endogenous Modulators on Host Inflammatory Response
Dr Stephen Getting is a pharmacologist working to unravel the biological effects of endogenous modulators (melanocortin peptides, urocortin, annexin 1 peptides) on the host inflammatory response, by looking at their ability to afford resolution of inflammation and cell protection. The aim of this research is to understand the mechanism of action of these compounds, via identification of pathways they modulate for downstream pharmacological manipulation and disease treatment.
Understanding how these anti-inflammatory and cytoprotective agents work will allow for a clearer understanding of their ability to exhibit early phase inhibition of cytokine release and a late induction of pro-resolving pathways. This research will allow for the potential development of novel therapeutics, to treat some of the biggest debilitating diseases including osteoarthritis.
Channelopathy of Cardiovascular Disease
Dr Kevin P Cunningham is investigating the biophysical states of ion channels and how this can be harnessed to selectively target conditions such as atrial fibrillation, pulmonary arterial hypertension, and pain. Recent work has focused on how the biophysical properties of the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel are altered in cardiac disease.
Previous related work includes a drug discovery programme, in collaboration with Merck Sharp & Dohme, utilising selective HCN inhibitors for the treatment of neuropathic pain.
Future work will involve investigating the voltage-gated potassium channel, Kv1.5 (KCNA5), and how it can be targeted in the treatment of atrial fibrillation. Some of the techniques used within this research include whole-cell patch clamp, in silico computational modelling, voltage clamp fluorometry, confocal microscopy and a range of molecular biology. Using in silico methods one can identify potential binding sites and screen novel compounds to those sites. The investigation is then moved in vitro, using whole-cell patch clamp to investigate the proposed site/compound and its effects on channel properties to attempt uncover novel therapeutic areas and further develop the One Health concept.
REDOX Signalling as a Biomarker for Human Aging-associated Disorders
Dr Aikaterini Anagnostopoulou is researching the role of REDOX signalling as a biomarker in aging-associated disorders with a focus on cancer, Type 2 Diabetes and neurological disorders. The main goal is to unravel the molecular mechanisms in aging-associated disorders in order to identify novel therapeutic targets to treat a plethora of human aging-associated diseases. This research mainly utilises molecular biology techniques, in vitro and invertebrate models of human disease, various tissues, proteomics and imaging/microscopy.
Disease Modelling and Drug Discovery using Caenorhabditis elegans
Dr Freddie Partridge's research is centred on the nematode model organism C. elegans, a system that allows us to use powerful genetic methods to understand disease biology. Work has involved making models of human genetic disease in C. elegans and investigating alpha-1-antitryspin deficiency liver disease and the roles of other serine protease inhibitors in disease.
Further work has involved the development of new tools for genetic and small molecular screening, establishing a system for high-throughput RNAi and compound screening in C. elegans and other organisms. This system is used for anthelmintic and insecticide discovery, toxicological assays, and phenotypic screening using models of human genetic disease. These tools can be used to address neglected tropical diseases, especially parasitic infectious disease.
Dr Freddie Partridge is collaborating with Prof Kathryn Else (Manchester), Prof Angela Russell (Oxford), and Prof David Sattelle (UCL) to develop new therapeutics for whipworm, a parasitic worm that infects around 500 million people.