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 Xudong Yang, Miss Jennifer Wood, Mr Benjamin Constant
Past: Dr Richard Salmon, Mr He Jiang, Mr Zhenquan Wei, Dr Aleksandra Lawera.
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
Key Publications
Full Publications at PubMed
1) Salmon RM, Guo J, Wood JH, Tong Z, Lawera, A, Yu M, Beech JS, Grainger DJ, Reckless, J, Morrell NW and Li W (2020) Molecular basis of ALK1-mediated signaling by BMP9/BMP10 and their prodomain bound forms. Nature Communications. 11, Article number: 1621
2) Hodgson J, ... Li W, Graf S, Upton PD and Morrell NW (2020) Characterisation of GDF2 mutations and levels of BMP9 and BMP10 in pulmonary arterial hypertension. Am J Respir Crit Care Med. 201:575-585.
3) Vacca M, ... Li W, Kostrzewski T, Leeming DJ, Ratziu, V, Allison MED, Anstee QM, Griffin JL, Oakley F and Vidal-Puig A (2020) Bone Morphogenetic protein 8B (BMP8B) tunes TGFb/BMP signaling in liver disease contributing to non-alcoholic steatohepatitis. Nature Metabolism, 2, 514-531.
4) Tong Z, Guo J, Glen RC, Morrell NW and Li W (2019) A bone morphogenic protein (BMP)-derived peptide based on the type I receptor binding site modifies cell-type dependent BMP signaling. Scientific Reports. 9, Article number: 13446.
5) 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 116: 17800-08.
6) 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, 47:779-91.
7) 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 Communication, 9: 1416.
8) Li W* and Huntington JA* (2012) Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a two-step recognition mechanism Blood. 120: 459-67. (*Joint corresponding author)
9) Yamasaki M, Li W, Johnson DJD and Huntington JA (2008) Crystal structure of a stable dimer reveals the molecular basis of serpin polymerisation. Nature, 455, 1255-8.
10) Li W, Adams TE, Nangalia J, Esmon CT and Huntington JA (2008) Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6Å structure of the heparin-bridged complex. Proc. Natl. Acad. Sci. USA, 105, 4661-6.
