Lalarukh Haris on the laboratory in which she is completing her PhD

https://doi.org/10.36866/pn.90.40

The Clinical Pharmacology Unit was founded in 1985 and is the pioneering example of the NHS funding academic developments in Cambridge. In 1998 we moved into our purpose-built clinical and basic science laboratories in the Addenbrooke’s Centre for Clinical Investigation (ACCI), funded by the British Heart Foundation (BHF) and an MRC Technology Foresight grant (jointly with Cardiovascular Medicine and Neurosurgery). Although our work is mostly academic, we have been strong protagonists of translational research since long before this became common practice. Many of our research outputs are being translated rapidly into advanced practices, mainly in hypertension. We give equal weight and importance to the clinical and non-clinical members of the unit, galvanizing the clinicians to learn basic science skills, and the scientists to contribute to patient-orientated research.

Research carried out in our group focuses on hypertension, arterial stiffness, genetics of sodium handling, ischaemia/reperfusion, and cardiovascular action of G-protein coupled receptors. In addition the unit undertakes teaching of undergraduates, postgraduates and junior doctors in clinical pharmacology and therapeutics.

The Clinical Pharmacology Unit has a strong record in clinical research. Clinical trials are run in the ACCI, the Clinical Investigation Ward and Vascular Research Clinics. We run large-scale clinical trials on drug therapy in hypertension and longitudinal collaborative studies investigating novel risk factors for cardiovascular disease (e.g. CHAOS, INSIGHT and ACCELERATE). We are accelerating usage of the imaging modalities PET-CT and MRI to understand and characterise conditions such as vascular inflammation, adrenal function and arterial stiffness. We use a number of
non-invasive techniques to investigate vascular and endothelial function.

I did my Master’s degree in the Department of Translational Medicine and Therapeutics in 2010, after which I decided to continue asking my research question in the form of a PhD. The people in my groups are engaging, helpful and motivating. Very recently I was encouraged to present a poster of my research at the British Pharmacological Society (BPS) in London and I was thrilled to win the Pfizer poster prize in the Clinical Pharmacology section.

My PhD, funded by the BHF, is supervised jointly between two eminent principal investigators in the unit. Morris Brown’s research is conducted in patients with Conn’s syndrome and phaeochromocytoma. He is inaugurating a BHF-funded programme of three trials investigating the role of renin measurement in the routine management of hypertension. Other current research projects include evaluation of 11C-metomidate scanning for lateralisation of Conn’s adenomas. He was awarded the Lilly Gold Medal by the BPS (2002) and the Walter Somerville Medal by the British Cardiac Society (2006). His introduction of the AB/CD rule, and innovations in management of phaeochromocytoma and Conn’s syndrome, led to the Hospital Doctors’ Award in 2003. In 2008 he co-hosted the International Symposium on Phaeochromocytoma in Cambridge.

Anthony Davenport’s research focuses on understanding the role of G-protein-coupled receptors (GPCRs) that are currently the targets for about half of drugs. We use in vitro pharmacology and in vivo imaging using PET, to determine how these receptors are altered with disease. Major interests include the role of the endothelin system in cerebrovascular disease and discovering the role of novel ‘orphan’ GPCRS, originally predicted to exist from the human genome but recently paired with their cognate transmitters (e.g. apelin, ghrelin, kisspeptins). We collaborate with the Wolfson Brain Imaging Centre to use PET to non-invasively image receptors in vivo using novel peptide and drug radioligands. Wider research interests are reflected through membership of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification.

My PhD joins the knowledge and techniques from both the groups. My research interest lies in investigating a novel G-protein coupled receptor and its role in regulating aldosterone and hypertension. Primary Hyperaldosteronism (PH) or Conn’s syndrome is the commonest curable cause of hypertension, affecting 5 to 15% of patients with the disease. In some patients with PH, benign tumours, which are formed in the adrenal gland(s), secrete aldosterone, the hormone which stimulates re-absorption of sodium ions in the distal nephron. In work carried out by the group we found that in a microarray comparison of aldosteronomas with their paired normal adrenals where 19,594 genes were screened, a cAMP coupled biogenic amine-like receptor; GPR61 was amongst the most significantly upregulated genes. Since GPR61 activation in vitro stimulates cAMP production, the major intracellular stimulus to aldosterone production, the hypothesise for my research is that GPR61 is a regulator of aldosterone which could be a novel therapeutic target for treatment of hypertension or other conditions associated with aldosterone regulation.