Our Division is interested in studying the actions of hormones (natural chemical messengers) in health and disease.
Diabetes is a group of conditions in which blood glucose levels rise, potentially leading to long term serious health problems such as heart attacks, strokes, kidney failure, blindness, limb gangrene and risk of amputation. Diabetes results from a deficiency of the hormone insulin (either in absolute or relative terms). Some people with diabetes have to inject insulin to control blood glucose, but it is challenging to get doses right without overshooting into low blood glucose (hypoglycaemia). We are interested in how this can be helped by structured education, the use of medical technology such as insulin pumps to deliver insulin, and glucose sensors to detect changes in blood glucose. We collaborate closely with Dr Roman Hovorka in the Metabolic Research Laboratories at the University of Cambridge, who is developing and clinically testing an artificial pancreas. We are also interested in how the brain detects falling blood glucose and how this may become altered in diabetes. Our aim is to help people with diabetes achieve better control of blood glucose safely without risk of hypoglycaemia, thus reducing the risk of long term complications.
Our Division also studies genetic and acquired disorders of the pituitary, thyroid and adrenal glands, and is recognised for its translational research in both rare (TSH-secreting pituitary tumours, acromegaly) and common (primary aldosteronism) endocrine conditions. A key focus in recent years has been the development and introduction in to routine clinical practice of molecular PET imaging to help guide personalised treatment in pituitary and adrenal neoplasia. This programme attracts referrals from across the UK and from many international centres. Our Division also studies the long-term endocrine sequelae of cranial irradiation for brain tumours (hypothalamic and pituitary dysfunction are common in this setting). Perhaps less expected in a clinical research setting, our Division also studies the endocrine and neural basis of financial decision making. As recent experience has shown, financial market bubbles and crashes can destabilise the global economy and a scientific explanation for risk behaviour might be helpful to understand how fluctuating levels of natural steroids contribute to this. Such studies provide clues as to why traders' testosterone levels rise during a bull market, and their cortisol levels rise during a bear market. These hormones have opposite effects, and both can amplify market changes.
Thyroid hormones are vital for fundamental processes including brain development, growth and controlling metabolic rate increase heart. Disorders therefore affect health, and research in our Division is focussed on nuclear hormone synthesis. It is studied in patients who have disorders that effect thyroid hormone metabolism and action. This includes resistance to Thyroid hormone and lipodystrophic (a disorder in which the body is unable to produce fat) insulin resistance associated with a specific gene defect that mediates lipid metabolism (PPARγ). Candidate genes and whole exome approaches are used to identify novel genetic aetiologies in these patients, and are accompanied by complementary studies that define their clinical phenotypes. Such research can be used to develop genetic tests and identify biomarkers that are used to form a national diagnostic service for rare and unusual thyroid disorders.
Lysosomes are found in nearly all animal cells and are responsible for recycling complex biological molecules and cell components. These activities are impaired in lysosomal diseases and cause wide-ranging effects that are clinically-recognised as specific diseases such as Gaucher, Krabbe, Fabry and Tay-Sachs disease. In our Division we study the causes of these. Studies include research into molecular targeting and the delivery of lysosomal proteins to their sites of action, the pathogenesis of lysosomal diseases, and the development of new therapeutic solutions to improve patient health. Indeed, several clinical trials of substrate reducing drugs and enzyme therapies are underway. These include gene therapies for diseases that affect the brain. They will enter clinical trials in 2019 – 2020, with early results expected from severe neurological diseases that affect babies and young children within their first 1 - 2 years after birth. With this same goal in mind, we have also developed authentic models of lysosomal disorders that affect the brain and can be used to assess the effects of therapeutic gene transfer. Ultimately this work will refine the interventions that are used to control the inflammation that results in brain injury by harnessing some of the most recent discoveries in immunity research.
Promising experiments are also underway to investigate the cause and treatment of B-cell proliferation and myelomatosis, which is a leading cause of death in patients with Gaucher’s disease. This guides therapies by predicting long-term risks in the light of clinical data and biomarkers that are present in blood plasma and cells. This work ensures optimal intervention before irreversible injury (including cancerous proliferation) occurs.