Developing p21 activated kinase-1 activating drug-like small molecules
- 1 April 2014 to 31 July 2015
- Awards: Pump-priming Awards
By combining advanced genetic manipulation technology with the state-of-the-art multi-scale electrophysiological and molecular approaches, Ming Lei’s current research focuses on cardiac ion channel function and its regulation under both physiological and pathophysiological conditions in a direction that will lead to a better understanding of hypertrophic and arrhythmic disorders, and the development of effective new therapeutic modalities. His team has made fundamental contributions for identification of the novel roles of a multifunctional enzyme-p21 activated kinase (Pak1) in the heart and discovered a new population of cardiomyocytes (named as Pnmt+ cell derived cardiomyocytes, PdCMs, derived from neuroendocrine cells in murine heart by using optogenetics approach. He has published ~100 peer-reviewed articles including those in top journals in cardiovascular and physiological fields such as Circulation, Circulation Arrhythm and Electrophysiol, Circulation Research, Cardiovasc Res, Journal of Physiol. As well as taking an active role in teaching in undergraduate and postgraduate programmes, He serves as a Senior Editor for Experimental Physiology (one of the society journals of the Physiological Society (UK), board member for Journal of Mol and Cell Cardiol and Associate Editor of Frontiers in Physiol etc. He has been invited to give keynote talks in various leading learned societies’ conferences including The Physiological Society, Australia Physiological Society, Chinese Physiological Society, International Society for Heart Research, International Union of Physiological Science.
Publications linked to this award:
- Wang Y, Wilson C, Cartwright EJ, Lei M*. Plasma membrane Ca2+ -ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse. J Physiol. 2017 595(24):7383-7398.
- Ni H, Wang Y, Crawford W, Zhang S, Cheng L, Zhang H, Lei M. Three-dimensional image reconstruction of distribution of Pnmt<sup>+</sup> cell-derived cells in murine heart. Sci Data. 2017 Sep 26;4:170134. doi: 10.1038/sdata.2017.134.
- Wang Y, Lin WK, Crawford W, Ni H, Bolton EL, Khan H, Shanks J, Bub G, Wang X, Paterson DJ, Zhang H, Galione A, Ebert SN, Terrar DA, Lei M. Optogenetic Control of Heart Rhythm by Selective Stimulation of Cardiomyocytes Derived from Pnmt+ Cells in Murine Heart. Sci Rep. 2017 Jan 13;7:40687. doi: 10.1038/srep40687.
- Egom EE, Kruzliak P, Rotrekl V, Lei M. The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue. J Cell Mol Med. 2015 Jul;19(7):1729-34.
- Wang Y, Tsui H, Bolton EL, Wang X, Huang CL, Solaro RJ, Ke Y, Lei M*. Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) homeostasis. Front Physiol. 2015;6:76..
- Lei M, Wang X, Ke Y, Solaro RJ. Regulation of Ca(2+) transient by PP2A in normal and failing heart. Front Physiol. 2015;6:13
- Ke Y, Wang X, Jin XY, Solaro RJ, Lei M. PAK1 is a novel cardiac protective signaling molecule. Front Med. 2014; 8(4):399-403. 2014
- Wang R, Wang Y, Zhang Y, Liu W, Huang K, Terrar DA, Solaro JR, Wang X, Ke Y and Lei M*. Inhibition of angiotensin II-induced cardiac hypertrophy and associated ventricular arrhythmias by a p21 activated kinase 1 bioactive peptide. PLOS One PLoS One. 2014;9(7):e101974.
- Wang Y, Tsui H, Liu W, Shi Y, Wang R, Zhang Y, Solaro R, Ke Y, Zhang H, Cartwright E, Wang X, Lei M*. P21 activated kinase-1 deficiency in cardiomyocytes increases in susceptibility to ventricular arrhythmogenesis in mice. Circulation: Arrhythm Electrophysiol Circ Arrhythm Electrophysiol. 2014 2014 Oct;7(5):938-48
- Davies L, Jin J, Shen W, Shi Y, Wu J, Zhang Y, Chen S, Dong L, Fraser J, Christoffels V, Huang, CLH. Zhang H, Ravens U, Cartwright E, Wang X* and Lei M*. Mkk4 deficiency in atrial cardiomyocytes increases in susceptibility to atrial arrhythmogenesis with age. J Am Heart Assoc 2014 2014 Apr 10;3(2):e000340. doi: 10.1161/JAHA.113.000340.
- Ke Y, Wang X, Jin XY, John Solaro R, Lei M. PAK1 is a novel cardiac protective signaling molecule. Front Med. 2014 Nov 22. [Epub ahead of print]
- Ke Y, Taglieri DM, Monasky MM, Scruggs NJ, Wang R, Wang Y, Geenen DL, Wang X, Lei M* and Solaro RJ. A p21 activated kinase activating peptide antagonizes angiotensin II-induced ventricular hypertrophy and fibrosis. Cardiovas Res 2014 (in revision)
- Egom EE, Mamas MA, Chacko S, Stringer SE, Charlton-Menys V, El-Omar M, Chirico D, Clarke B, Neyses L, Cruickshank JK, Lei M*, Fath-Ordoubadi F. Serum sphingolipids level as a novel potential marker for early detection of human myocardial ischaemic injury. Front Physiol. 2013;4:130.
- Wu J, Zhang Y, Zhang X, Cheng L Lammers W Grace A, Fraser J, Zhang H, Huang, CLH. & Lei M*. Sinatorial node function and intracardiac conduction in a murine model of long QT syndrome type 3. Am J Physiol (Heart Circ Physiol). 2012 302:H1510-23.
- Huang, CLH, Lei L, Matthews G, Zhang Y, Lei M*. Pathophysiological mechanisms of cardiac conduction disease associated with SCN5A deficiency: insights from mouse models. Front Physiol. 2012;3:234.
- Liu W, Zi M, Naumann R Ulm S, Jin J, Taglieri DM; Prehar S, Gui J, Tsui H, Xiao R, Neyses L, Solaro RJ, Ke Y, Cartwright EJ*, Lei M* & Wang X*. Pak1 as a Novel Therapeutic Target for Anti-Hypertrophic Treatment in the Heart, Circulation. 2011;124:2702-15.
- Hao X, Zhang Y, Zhang X, Nirmalan M, Davies L, Konstantinou D, Fei T, Dobrzynski H, Wang X, Grace A, Zhang H, Boyett M, Huang C and Lei M*. TGF-1 mediated fibrosis and ion channel remodeling are key mechanisms producing the sinus node dysfunction associated with SCN5A deficiency and aging. Circulation A & E. 2011 4:397-406.
- Egom EE, Tamer M. Mohamed A, Mamas M, Chirico D, Stringer SE, Ke Y, Wang T, Chacko S, Solaro J, Ordoubadi F, Cartwright JE, Lei M*. Activation of Pak1/Akt/eNOS signaling following S1P release as part of a mechanism protecting cardiomyocytes against hypoxic or ischemic cell injury. Am J Physiol (Heart Circ Physiol) 2011,301:H1487-1495.
- Kharche S, Yu J, Lei M* and Zhang H*. A biophysically detailed mathematical model of the mouse sino-atrial node. Am J Physiol (Heart Circ Physiol). 2011; 301:H945-63.
- Zhao Z, Chen Z, Zhao X, Pan F, Cai M, Wang T, Zhang H, Lu JR, Lei M*. Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions. J Biomed Sci. 2011 18:37.
- Butters TD, Aslanidi OV, Inada S, Boyett MR, Hancox JC, Lei M*, Zhang H*. Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaker in sick sinus syndrome. Circ Res. 2010; 107: 126-37.
- Gui J, Wang T, Jones RP, Trump D, Zimmer T, Lei M*. Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010; 5: e10985. IF: 4.1, C: 0
- Egom EE, Ke Y, Musa H, Mohamed TM, Wang T, Cartwright E, Solaro RJ, Lei M*. FTY720 prevents ischemia/reperfusion injury-associated arrhythmias in an ex vivo rat heart model via activation of Pak1/Akt signaling. J Mol Cell Cardiol. 2010; 48: 406-14.
- Gui J, Wang T, Trump D, Zimmer T, Lei M*. Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. J Cardiovasc Electrophysiol. 2010; 2: 564-73.
- Eroume A Egom, Ke YB, Solaro RJ and Lei M*. Mechanisms of cardioprotection in ischemia/reperfusion injury: spotlight on sphingosine-.1-phosphate and bradykinin signalling. Prog Biophys Mol Biol. 2010;103:142-7.