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Prof Lucie Clapp
Room 324
Institute of Cardiovascular Science
Rayne Building, 5 University Street
London
WC1E 6JF
Tel: 020 7679 6180
Appointment
  • Professor Vascular Physiology
  • Centre for Cardiovascular Genetics
  • Institute of Cardiovascular Science
  • Faculty of Pop Health Sciences
Biography

Lucie Clapp is a trustee of UCL, sitting on the governing body (Council) responsible for approving the academic strategy and business plans of the university. She is also Professor of Vascular Physiology at the Institute of Cardiovascular Science. She graduated in Pharmacology (2:1) from Bristol University and received her PhD from St Georges' Hospital Medical School, London. She was a postdoctoral fellow and Instructor in Physiology at the University of Massachusetts Medical School, USA (1985-1988) before returning to the Pharmacology Department at St Thomas' Hospital in London. She joined the UCL Division of Medicine in 1996, was appointed Reader in 2002, Professor in 2006 and elected onto Council by the professorial membership of Academic Board in 2015.


Professor Clapp is committed to student welfare, serving as a postgraduate tutor and mentor for several years at UCL and has been co-organiser of the British Heart foundation 4 year PhD programme since 2009. She teaches on several undergraduate and postgraduate courses (7) and demonstrates leadership in teaching, founding and directing a new undergraduate iBSc programme in Cardiovascular Science for 3rd year medics.


A pharmacologist and biophysicist by training, Professor Clapp has won numerous awards and accolades for her research on prostacyclins and the functional properties of ion channel proteins in smooth muscle. She was awarded the Howard Sprague Fellowship from the American Heart Association (AHA) for the best application in the State of Massachusetts, a Career Development Award from the Welcome Trust and two Senior Fellowships from the Medical Research Council (1996-2006). In recognition of her contribution, she was elected Fellow of the AHA in 2001, Fellow of the Pulmonary Vascular Research Institute (PVRI) in 2010, Fellow of the Royal Society of Biology in 2011, and to the International Union of Basic and Clinical Pharmacology Committee responsible for Receptor Nomenclature and Drug Classification of prostanoid receptors in 2016. 


Professor Clapp has authored many papers in top peer-reviewed journals, including PNAS, Circulation Research, Lancet, Am J Respir Crit Care Med and Circulation as well as writing book chapters, editorials, documents for the Food and Drug Administration (FDA) and materials for Continuing Medical Education (CME) credits for Physicians. She has lectured around the world at symposia organised by the American College of Chest Physicians, European Respiratory Society, International Society for Heart and Lung Transplant, Intensive Care and Emergency Medicine, European Society of Cardiology, PVRI and International School of Pharmacology.  She has served on numerous review panels for journals and grant awarding bodies and acted as an editor for British Journal of Pharmacology (2009-2015).


Experimental Medicine is at the forefront of Professor Clapp’s activities, being involved in the first clinical use of terlipressin in sepsis and the identification of a new clinical syndrome associated with drug-induced hyperkalemia. She was the driving force behind setting up the UCL-wide pulmonary arterial hypertension (PAH) consortium, bringing together clinicians and scientists from across UCL’s partner hospitals. This consortium is linked nationally through the National Cohort Study of Idiopathic and Heritable PAH (BRIDGE project), and internationally through the PVRI. Professor Clapp sits on the IPAH Cohort Study Governance Committee and the PVRI Preclinical & Molecular Science Task Force. Through consultancies and grants, she has interacted for over 20 years with Pharmaceutical and USA Biotech companies in the pulmonary hypertension field, bringing an understanding of the commercial world alongside research.  

Research Summary

Overall summary of research
In the last decade, our group has principally been involved in elucidating the biophysical and functional properties of vascular potassium channels with a strong emphasis on their roles in sepsis, vascular remodelling and pulmonary hypertension. Work has specifically focused on in vitro and in vivo models of septic shock in rodents and humans, the biochemistry and confocal imaging of calcineurin and its role in mediating smooth muscle proliferation as well as the mechanistic basis underlying the therapeutic effects of prostacyclins in pulmonary arterial hypertension (PAH). Complimenting these are studies in patients to establish biomarkers of early disease (smooth muscle hypertrophy) and the impact of prostacyclin therapy on a broader range of markers of endothelial dysfunction and inflammation in PAH.


Prostacyclin signalling through membrane and nuclear receptors
In collaboration with Prof Howarth and Dr Hall (ICH/GOSH) and Prof Morrell (Cambridge) we are exploring cellular mechanisms underlying abnormal cell growth in lung cells derived from patients with PAH in addition to the impact of prostacyclin therapy on this process. Interestingly, we have found in PAH that prostacyclin signalling is disrupted in pulmonary smooth muscle cells, switching away from the classical IP receptor and cyclic AMP driven pathway, to one involving the nuclear transcription factor, PPARy. The mechanism of PPARy activation by prostacyclin is unknown but we are exploring whether it inhibits growth through an impact on the NFAT/calcineurin pathway. In biochemical studies funded in partnership with United Therapeutics (USA) and Prof Whittle (William Harvey, Barts), we have very recently established that the prostacyclin analogue treprostinil has a novel pharmacology compared with other agents in its class like iloprost, activating both DP1 and EP2 receptors in the nanomolar range. These receptors therefore represent previously unrecognised targets for this agent, and suggest that the overall beneficial pulmonary vasorelaxant profile and other pharmacological actions of treprostinil, especially in diseases where the IP receptor is down-regulated, may contribute to its therapeutic efficacy. It remains to be determined how these findings impact on selexipag, a selective non prostanoid IP receptor agonist, currently in phase III clinical trials in PAH.

Calcineurin interaction with KATP channels

Our lab has been instrumental in showing that the calcium-dependent phosphatase, calcineurin is a key regulator of the ATP-sensitive potassium (KATP) channel. In collaboration with Prof Tinker (UCL and Barts and the London) we have shown that the molecular basis for this regulation involves dephosphorylation of channel subunits, and that such a mechanism, is likely to directly oppose the action of vasodilators which open this channel through phosphorylation. We and others have demonstrated that excessive opening of the vascular KATP channel is implicated in the vasodilation and vascular hyporeactivity that underlies septic shock, though despite this, therapeutic channel inhibition using sulfonylurea agents like glibenclamide has proved disappointing in humans. Our recent observations that sympathetic activity, which is often high in septic patients, may actually be helping maintain blood pressure by keeping the channel closed, could therefore explain lack of efficacy of channel inhibitors in sepsis. Studies in the future are planned to more fully understand the influence of sympathetic tone on in vivo KATP channel function and blood pressure, where the regulation may ultimately be determined by calcineurin activity.

Teaching Summary

I teach across 3 different Faculties at UCL on several BSc and MSc/MRes courses run in the Institute of Cardiovascular Science, Division of Medicine, Department of Neuroscience, Physiology & Pharmacology, and in Biochemistry. I am founder and director of the newly created IBSc in Cardiovascular Science, chair of the Exam Board for the equivalent MSc course and co-organiser of the 4 Year BHF PhD programme for which I am a co-applicant on the recent successful renewal of this PhD scheme in Aug 2016. Teaching activities are summarised below:

1. Integrated BSc in Cardiovascular Science for 3rd Year medical students
I have designed this course to give a contemporary scientific view of cardiovascular disease. Students will develop an understanding of the etiology, diagnosis and clinical management of common cardiovascular diseases through case-based, team work and class discussions. The course starts in Sept 2016. 

2. Heart & Circulation for 3rd year iBS/BSc (PHOL3002) and MSc (PHOLG043) students
I have been director of this module since 2013 and co-organise it with Prof Alun Hughes. Approximately 80 students take this highly popular course - a series of lectures (22 in total) and tutorials covering physiology and pathophysiology with special reference to the human heart and circulation. I run the lab-based organ bath pharmacology and blood pressure practicals and teach on a range of topics, including vascular potassium channels, smooth muscle contraction and animal models of cardiovascular disease. 

3.MSc in Cardiovascular Science
I lecture on animal models of pulmonary hypertension, including covering the genetic basis of this disease (CARDG02). I set in course essays and am on the teaching committee which oversees the course. 

4. BHF 4 Year PhD programme (since 2009)
For the next 5 years, 4 students will be appointed each year to engage in research in any area of cardiovascular biomedicine at UCL. I am involved in interviewing, mentoring, helping students choose appropriate rotation projects, and overseeing their 1st year assessments of each rotation project. 

5. 3rd Year BSc/iBSc students (PHOL3902 & PHOL3904)
This involves supervising laboratory research and library projects based around sepsis & pulmonary hypertension, examining student oral presentations and marking dissertations.

6. Biochemistry of Cardiovascular Disease (BIOC3011) & Cell Signalling in Health & Disease (PHOL3004)
I lecture on vascular remodelling in diseases such systemic hypertension and atherosclerosis and how endothelial dysfunction drives the pathophysiology (BIOC3011). In PHOL3004, I teach how the hormone prostacyclin can signal in cells through membrane and nuclear receptors. I set and mark in-course exam questions, and run a journal club. 

7. Drug Discovery (MEDCG004)
Includes lecturing on the pathobiology of pulmonary hypertension and the molecular targets for potential future novel treatments; the setting and marking of exam/essay questions.

8. International teaching
Teaching in symposia with CME (Continuing Medical Education) credits for organisations like the International Society for Heart and Lung Transplantation, American College of Chest Physicians and European Respiratory Society. Providing online materials to global pharmaceutical companies as well as to ACCME and companies including AKH Inc, both accreditation providers of continuing education for licensed health care specialists in the USA.

Academic Background
1985 PhD Doctor of Philosophy – Pharmacology University of London
1981 BSc Bachelor of Science – Pharmacology University of Bristol
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