BHF Lecturer in Vascular Biology
Pulmonary arterial hypertension
Websites:
Research themes
Departments and Institutes
Research Interests
Molecular basis of TGFß/BMP signalling in cardiovascular diseases
We study how dysfunction of endothelial BMP signalling pathways leads to cardiovascular diseases, with the aim of developing therapeutic reagents targeting pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia by manipulating these signalling complexes.
The focus of the group is on BMP9(10):ALK1:BMPRII pathways, their interactions with endoglin and TGFß pathways. We use multidisciplinary approaches including protein crystallography, biochemical, biophysical and cellular assays using control as well as patient derived primary cells.
Group members:
Current: Dr Zhen Tong, Dr Jingxu Guo, Dr Aleksandra Lawera, Miss Jennifer Wood
Past: Dr Richard Salmon, Mr He Jiang, Mr Zhenquan Wei
Keywordscell signalling ; pulmonary arterial hypertension ; structural biology ; protein biochemistry |
Topics
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Collaborators
Collaborators outside this directory
- Professor Alison Condliffe - University of Sheffield
- Prof. Steve Charnock-Jones - Department of Obstetrics and Gynaecology, University of Cambridge
- Prof Helen Arthur - Institute of Genetic Medicine, Newcastle University
- Dr Minmin Yu - MRC-LMB
- Professor Peter ten Dijke - Leiden University Medical Center
Key Publications
Lawera, A, Tong, Z, Thorikay, M, Redgrave, RE, Cai, J, van Dinther, M, Morrell, NW, Afink, GB, Charnock-Jones, DS, Arthur, HM, ten Dijke, P and Li, W (2019) Role of Soluble Endoglin in BMP9 Signaling. Proc. Natl. Acad. Sci. USA In press.
Wood, JH, Guo, JX, Morrell NW and Li W (2019) Advances in the molecular regulation of endothelial BMP9 signalling complexes and implication for cardiovascular disease. Biochemical Society Transactions, 47:779-791.
Morrell NW, Upton PD, Li W and Yu PB (2019) Letter Regarding Article, “Selective BMP-9 inhibition partially protects against experimental pulmonary hypertension”. Circ Res. 124: e81
Guo J, Lodge K, Newnham M, Bunclark K, Toshner M, Morrell NW and Li W (2018) Increased anti-elastase activity in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Am J Rep Cell Mol. 59: 652-55.
Graf S, Haimel M, Bleda M, Hadinnapola C, Southgate L, Li W, et al. (2018) Identification of rare sequence variation underlying heritable pulmonary arterial hypertension Nat Commun, 9: 1416.
Li W*, Salmon RM, Jiang H & Morrell NW (2016) Regulation of the ALK1 ligands, BMP9 and BMP10 Biochemical Society Transactions 44: 1135-41.
The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension. Ormiston ML, Upton PD, Li W, Morrell NW. Glob Cardiol Sci Pract. 2015 Nov 17;2015(4):47.
The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells. Jiang H, Salmon RM, Upton PD, Wei Z, Lawera A, Davenport AP, Morrell NW, Li W. J Biol Chem. 2016 Feb 5;291(6):2954-66.
Regulation of bone morphogenetic protein 9 (BMP9) by redox-dependent proteolysis. Wei Z, Salmon RM, Upton PD, Morrell NW, Li W. J Biol Chem. 2014 Nov 7;289(45):31150-9.
BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Wooderchak-Donahue WL, McDonald J, O'Fallon B, Upton PD, Li W, Roman BL, Young S, Plant P, Fülöp GT, Langa C, Morrell NW, Botella LM, Bernabeu C, Stevenson DA, Runo JR, Bayrak-Toydemir P. Am J Hum Genet. 2013 Sep 5;93(3):530-7.
Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a 2-step recognition mechanism. Li W*, Huntington JA*. Blood. 2012 Jul 12;120(2):459-67.
Bone morphogenetic protein type II receptor mutations causing protein misfolding in heritable pulmonary arterial hypertension. Li W, Dunmore BJ, Morrell NW. Proc Am Thorac Soc. 2010 Nov;7(6):395-8.
Thrombin inhibition by serpins disrupts exosite II. Li W, Johnson DJ, Adams TE, Pozzi N, De Filippis V, Huntington JA. J Biol Chem. 2010 Dec 3;285(49):38621-9.
Adams, TE, Li W and Huntington JA (2009) Molecular basis of thrombomodulin activation of slow thrombin. J Thromb Haemost. 7, 1688-95.
Structural insights into the multiple functions of protein C inhibitor. Huntington JA, Li W. Cell Mol Life Sci. 2009 Jan;66(1):113-21.
The heparin binding site of protein C inhibitor is protease-dependent. Li W, Huntington JA. J Biol Chem. 2008 Dec 19;283(51):36039-45.
Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Yamasaki M, Li W, Johnson DJ, Huntington JA. Nature. 2008 Oct 30;455(7217):1255-8.
Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complex. Li W, Adams TE, Nangalia J, Esmon CT, Huntington JA. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4661-6.
Structure of native protein C inhibitor provides insight into its multiple functions. Li W, Adams TE, Kjellberg M, Stenflo J, Huntington JA. J Biol Chem. 2007 May 4;282(18):13759-68.
Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation. Johnson DJ, Langdown J, Li W, Luis SA, Baglin TP, Huntington JA. J Biol Chem. 2006 Nov 17;281(46):35478-86.
Expression and characterization of full-length human huntingtin, an elongated HEAT repeat protein. Li W, Serpell LC, Carter WJ, Rubinsztein DC, Huntington JA. J Biol Chem. 2006 Jun 9;281(23):15916-22.
Johnson DJ, Li W, Adams TE, Huntington JA. (2006) Structure of Antithrombin-factor Xa S195A-heparin reveals the allosteric mechanism of antithrombin activation. EMBO J. 25(9):2029-37.
Crystal structure of wild-type human thrombin in the Na+-free state. Johnson DJ, Adams TE, Li W, Huntington JA. Biochem J. 2005 Nov 15;392(Pt 1):21-8.
Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Li W, Johnson DJ, Esmon CT, Huntington JA. Nat Struct Mol Biol. 2004 Sep;11(9):857-62.
Highly discriminating protein-protein interaction specificities in the context of a conserved binding energy hotspot. Li W, Keeble AH, Giffard C, James R, Moore GR, Kleanthous C. J Mol Biol. 2004 Mar 26;337(3):743-59.
