Molecular Mechanisms and Therapeutics

The Molecular Mechanisms & Therapeutics (MMT) Sub-Group focuses on translational research, from identification of molecular targets to therapeutic applications, for a wide range of medical conditions. Collaborating with researchers in the Centre for Living, this work utilises multidisciplinary cellular, imaging & molecular biology techniques, animal models and clinical tissues to understand and treat the following conditions:

Wound healing & skin conditions

Dr Patricia Martin and Dr Catherine Wright use human skin from psoriatic, diabetic and non-diabetic biopsies (available from GCU Skin Tissue Bank) and connexin transgenic mice to investigate the potential of connexins as therapeutic targets for inflammatory skin disorders including, non-healing wounds and psoriasis. Additionally, Dr Wright has interests in the IGFBP superfamily effects in wound healing and extracellular matrix deposition. Work by the team also links with the Public Health & Infections sub-group, through research on the role of the microbiome in diabetic foot disease in collaboration with Dr Janice Spencer.

Diabetes & Cardiovascular disease

Prof Ann Graham’s work focuses on factors contributing to dysregulation of lipid and lipoprotein metabolism in a number of differing contexts, including atherosclerosis.  A recently completed (Sept 2020) translational project, funded by Heart Research UK, studied microRNA sequences involved in macrophage ‘foam’ cell formation; other studies have examined the role of mitochondrial, endosomal and cytosolic lipid transporters in regulating intracellular lipid metabolism.  Drs Martin and Wright also apply their knowledge of connexin and IGF signalling to pulmonary hypertension and diabetic wound healing. Researchers in this area have strong links with the Cardiovascular Disease and Long Term Conditions: Diabetes & Metabolism sub-groups.

Cancer

Using primary acute myeloid leukaemic (AML) cells and various AML cell lines, primary blood monocyte-derived macrophages, and advanced 3D (spheroid) in vitro co-culture systems, Dr Mark Williams investigates the pathological mechanisms underlying AML and Multiple Myeloma, including the role of bone marrow resident cells in mediating chemoresistance to treatments for these blood cancers, with a focus on ERK1/2, STAT3 and MCL-1 signalling.

Neurological conditions

Aligning thematically with the Ageing WellLiving with Stroke and Vision Sciences Research Groups, research on a wide range of neurological conditions is conducted within MMT, using pioneering patient-derived neuronal cultures, neuronal & retinal cell lines and mouse, rat and zebrafish models of disease. Several researchers study the molecular basis of Alzheimer’s disease, including links with ageing (Dr Fiona Kerr & Dr Gillian Hunter), Nrf2 (Dr Kerr), UBA1 (Dr Hunter), and lipid metabolism (Prof Graham & Dr Xinhua Shu). Dr Hunter has expertise in the study of Spinal Muscular Atrophy, focussing on the role of UBA1 & CYTSB in the multi-system pathogenesis of this condition. Dr Shu has specific interests in the role of cholesterol metabolism in retinal diseases including age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa, with a focus on oxidative stress and inflammation. Additionally, Dr Sharron Dolan studies the neuronal mechanisms of pain and analgesia, applying this knowledge to neuropathic pain in diabetes & obesity.

Infectious diseases

Prof Linda Scobie has expertise in viral zoonoses and the contribution of viruses to chronic conditions including xenotransplantation, liver disease and inflammatory disorders. Prof Scobie also has interests in emerging infections and food-borne pathogens, in collaboration with Dr Claire Crossan and researchers in the Public Health & Infections sub-group.