Morrell


Nick Morrell’s laboratory¬†studies the molecular mechanisms underlying pulmonary arterial hypertension. In particular our research is focussed on how mutations in the bone morphogenetic protein type II receptor (BMPR-II), a receptor member of the transforming growth factor-beta superfamily, cause familial pulmonary arterial hypertension (PAH). Our research is revealing dysfunctional signalling, gene transcription and cell biology in vascular cells as a consequence of BMPR-II mutation. Achievements to date include: i) determination that BMPR-II mutations affect receptor function by diverse molecular mechanisms, but all mutations lead to a critical reduction in the Smad1/5 signalling pathway and reduced transcription of Smad responsive genes; ii) delineation of a model of PAH pathogenesis in which BMPR-II mutations promote proliferation of pulmonary artery smooth muscle cells but promote apoptosis of pulmonary artery endothelium; iii) identification that dysfunction of BMPR-II is involved in the pathogenesis of more common forms of PAH; iv) establishment of animal genetic models that have shown the requirement for, and mechanisms of, additional environmental or genetic hits in the pathogenesis of PAH; v) identification of novel targets for therapy, including inhibitors of the TGF-beta and PDGF pathways.¬† Our research is demonstrating the broader role of the BMP pathway in vascular disease and providing new insights into the pathogenesis of other conditions characterised by abnormal tissue repair. Our group has close links with the Pulmonary Vascular Diseases Programme at Papworth Hospital, where Professor Morrell is the Research Director. We have an active translational research programme at Papworth where new targets identified from basic science studies can be trialed for the first time in patients with severe PAH.¬† Additional research themes in the Morrell laboratory are elucidating the molecular basis of hypoxic signalling in pulmonary vascular cells, as well as the molecular pharmacology of G-protein coupled receptor and adenylyl cyclase signalling in pulmonary vascular cells. A new programme of research is being developed to exploit the opportunity provided by the large referral base of thromboembolic pulmonary hypertension patients at Papworth Hospital. This includes genetic studies of candidate genes involved in coagulation and fibrinolytic pathways in these patients, as well as cell and tissue based studies of vascular remodelling in this important but neglected condition.

BIOGRAPHY
Nick Morrell is Reader in Respiratory Medicine and Professor of Cardiopulmonary Medicine at University of Cambridge School of Medicine. He is Honorary Consultant Physician at Addenbrooke’s and Papworth Hospitals.Professor Morrell’s major research interest is in pulmonary vascular disorders. His interests span from genetic and molecular mechanisms of familial and idiopathic pulmonary arterial hypertension to TGF-beta signaling, experimental therapies for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

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