Centre for Cardiovascular Physiology and Pharmacology

Lead: Professor Lucie Clapp

Group Members: Dr Jigisha Patel (Post Doc), Dr Lei Shen (Post Doc), Dr Rijan Gurung (Post Doc), Dr Mohammad Eddama (Clinician), Dr Nelson Orie (Senior Research Associate), Christina Picken (PhD student), Jerries Abu-Hanna (PhD student), Hamda Aboujassoum (UCL Non-resident PhD Student), Dr Jay Acharya (Laboratory Manager)

Professor Clapp, a pharmacologist and biophysicist by training, has expertise in the functional properties of potassium channels and prostaglandins in the cardiovascular system, particularly their role in bacterial infection and blood vessel remodelling. Grants from Research Councils and Charities have underpinned this work, including from the MRC, BBSRC, British Heart Foundation (BHF) and Welcome Trust. Through knowledge-transfer partnerships and consultancies, we have interacted with several Pharmaceutical companies over the last 20 years, raising funds to develop novel therapeutic strategies for treating pulmonary atrial hypertension (PAH), a devastating lung disease. Currently the laboratory is involved in defining the pharmacology and cellular action of drugs in clinical testing (BPS-314d-MR and Ralinepag) or FDA approved (treprostinil), using novel polymer chemistry approaches to improve drug targeting to the lung and exploring ways microvesicles can be used be as biomarkers of disease and treatment efficacy in PAH and cancer. These studies involve collaborations with UCLPartner and European (Bichat, Rome & Aarhus) hospitals as well as USA Biotechnology Companies, QMCL and Nottingham University.

Our laboratory is engaged in many teaching activities, including running an IBSc programme in Cardiovascular Science, a popular Heart & Circulation BSc course, and supporting the UCL PhD programmes funded by the BHF and Qatar Government. The latter scheme in particular aspires to help women in Qatar achieve leadership in biomedical science.

Highlights

Key Achievements:

1. The prostacyclin (IP) receptor is down regulated in patients with pulmonary arterial hypertension (PAH) and non IP-receptor signalling via the nuclear transcription factor, PPARγ becomes a prominent mechanism by which prostacyclin analogues can promote anti-proliferative effects in PAH.
2. Treprostinil has unique pharmacology amongst the prostacyclin class of drugs that are used in the treatment of pulmonary arterial hypertension, and can activate both human prostaglandin DP1 and EP2 receptors at clinically relevant (nanomolar) doses.
3. Potassium channels play a fundamental role in meditating vascular hyporeactivity in sepsis with the calcium-dependent phosphatase, calcineurin being a fundamental regulator of the ATP-sensitive potassium channel, modulating both blood pressure and serum potassium levels in humans.

Key publications:

• Clapp LH & Gurung R, (2015). The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: Role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 120:56-71.
• Bubb KJ, Trinder SL, Baliga RS, Patel, JA, Clapp LH, MacAllister RJ, Hobbs AJ, (2014). Inhibition of phosphodiesterase 2 augments cGMP and cAMP signalling to ameliorate pulmonary hypertension. Circulation 130:496-50.
• Whittle BJ, Silverstein A, Mottola D, Clapp LH, (2012). Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: Treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 84:68-75.
• Falcetti E, Hall SM, Phillips PG, Patel JA, Morrell NW, Haworth SG, Clapp LH, (2010). Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med, 182:1161-70.
• Singer M, Coluzzi F, O'Brien AJ, Clapp LH, (2005). Reversal of life-threatening, drug-related potassium-channel syndrome by glibenclamide. Lancet. 365:1873-1875.

Contact details:

3rd Floor, Rayne Building 
5 University Street
London WC1E 6JF

Professor Lucie Clapp
Email: l.clapp@ucl.ac.uk
Tel: 020 7679 6180 (internal 46180)

Dr Jay Acharya
Email: j.acharya@ucl.ac.uk