Department of Cell Biology
Education and Training
Ph.D., McGill University
Postdoctoral Fellow, Howard Hughes Medical Institute, Children’s Hospital, Harvard Medical School
Office: ARB G024
263 Farmington Avenue
Farmington, CT 06030
Calcium is the most common signal transduction element in virtually all cells ranging from bacteria to neurons. Recent studies have demonstrated the importance of transient receptor potential (TRP) channels in mediating calcium signals. The mammalian TRP channel superfamily consists of a diverse group of calcium permeable nonselective cation channels that may play a role in pain transduction, thermo-sensation, mechanotransduction, tumor suppression, vasodilatation, and neurodegenerative disorder. Twenty-eight mammalian TRP channel genes have been cloned since the first TRP channel protein was identified in Drosophila , yet their physiological functions are to be revealed.
We are interested in calcium signaling mechanisms and their potential roles under physiological and pathological conditions. We apply a multidisciplinary approach to study the potential functions of the calcium-permeable TRP channels. We use molecular biology and biochemistry approaches to identify channel proteins and the associated partners; we use patch-clamp to study channel functions and gating mechanisms; and we use in vivo transgenic animal models to investigate physiological or pathological functions of the TRP channels.
Our current research projects include:
- TRP channels and calcium signaling mechanisms in cardiac fibrogenesis.
- Gating mechanism and physiological functions of TRPM7 and TRPM6, the two channel-kinase proteins that exhibit both channel functions and protein kinase activities.
- Gating mechanisms and potential roles of TRPM2
Curry EJ, Ke K, Chorsi MT, Wrobel KS, Miller AN 3rd, Patel A, Kim I, Feng J, Yue L, Wu Q, Kuo CL, Lo KW, Laurencin CT, Ilies H, Purohit PK, Nguyen TD. Biodegradable Piezoelectric Force Sensor. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):909-914. doi: 10.1073/pnas.1710874115. Epub 2018 Jan 16. PMID: 29339509.
Park JW, Yan L, Stoddard C, Wang X, Yue Z, Crandall L, Robinson T, Chang Y, Denton K, Li E, Jiang B, Zhang Z, Martins-Taylor K, Yee SP, Nie H, Gu F, Si W, Xie T, Yue L, Xu RH. Recapitulating and Correcting Marfan Syndrome in a Cellular Model. Int J Biol Sci. 2017 Apr 10;13(5):588-603. doi: 10.7150/ijbs.19517. eCollection 2017.PMID:28539832.
Yu H, Kistler A, Faridi MH, Meyer JO, Tryniszewska B, Mehta D, Yue L, Dryer S, Reiser J. Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates Proteinuria. J Am Soc Nephrol. 2016 Nov; 27(11):3308-3319. Epub 2016 Mar 28. PMID: 27020855.
Zeng H, Guo M, Zhou T, Tan L, Chong CN, Zhang T, Dong X, Xiang JZ, Yu AS, Yue L, Qi Q, Evans T, Graumann J, Chen S. An Isogenic Human ESC Platform for Functional Evaluation of Genome-wide-Association-Study-Identified Diabetes Genes and Drug Discovery. Cell Stem Cell. 2016 Sep 1; 19(3):326-40. doi: 10.1016/j.stem.2016.07.002. Epub 2016 Aug 11.PMID: 27524441.
Tsujikawa H, Yu AS, Xie J, Yue Z, Yang W, He Y, Yue L. Identification of key amino acid residues responsible for internal and external pH sensitivity of Orai1/STIM1 channels. Sci Rep. 2015 Nov 18;5:16747. doi: 10.1038/srep16747. PMID: 26576490.
Yue Z., Xie J., Yu A, Stock J, Du J, Yue L. Role of TRP channels in the cardiovascular system. Am J Physiol Heart Circ Physiol. 2015 Feb 1;308(3):H157-82. doi: 10.1152/ajpheart.00457.2014
Cagavi E, Bartulos O, Suh C, Sun B, Yue Z, Jiang Z, Yue L, Qyang Y. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation. PlosOne. 2014. Dec. 18.
Qin X, Yue Z, Sun B, Yang W, Xie J, Ni E, Feng Y, Mahmood R, Zhang Y, Yue L. Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels. Br J Pharmacol. 2013 Mar;168(6):1294-312. (See commentary by Rohacs T. Sphingosine and the transient receptor potential channel kinase(s). Br J Pharmacol. 2013 Mar;168(6):1291-3).
Yue Z, Zhang Y, Xie J, Jiang J, Yue L.Transient Receptor Potential (TRP) channels and cardiac fibrosis. Curr Top Med Chem. 2013 Feb 13. [Epub ahead of print].
Ge X, Ren Y, Bartulos O, Lee MY, Yue Z, Kim KY, Li W, Amos PJ, Bozkulak EC, Iyer A, Zheng W, Zhao H, Martin KA, Kotton DN, Tellides G, Park IH, Yue L, Qyang Y. Modeling supravalvular aortic stenosis syndrome with human induced pluripotent stem cells. Circulation. 2012; 126(14):1695-1704.
Lee MY, Sun B, Schliffke S, Yue Z, Ye M, Paavola J, Bozkulak EC, Amos PJ, Ren Y, Ju R, Jung YW, Ge X, Yue L, Ehrlich BE, Qyang Y. Derivation of functional ventricular cardiomyocytes using endogenous promoter sequence from murine embryonic stem cells. Stem Cell Res. 2012;8(1):49-57
Estes NA 3rd, Sacco RL, Al-Khatib S, Ellinor P, Bezanson J, Alonso A, Antzelevitch C, Brockman RG, Chen P, Chugh S, Curtis A, Dimarco J, Ellenbogen K, Epstein A, Ezekowitz M, Fayad P, Gage B, Go A, Hlatky M, Hylek E, Jerosch-Herold M, Konstam M, Lee R, Packer D, Po SS, Prystowsky EN, Redline S, Rosenberg Y, Van Wagoner DR, Wood KA, Yue L, Benjamin EJ. American Heart Association Atrial Fibrillation Research Summit: A Conference Report From the American Heart Association. Circulation. 2012 Oct 2;126(14):1695-704
Yue L, Xie J, Nattel S. Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation. Cardiovasc Res. 2011; 89(4):744-53
Xie J, Sun B, Du J, Yang W, Chen HC, Overton JD, Runnels LW, Yue L. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) controls magnesium gatekeeper TRPM6 activity. Sci Rep. 2011;1:146. P1-11. Epub 2011
Du J, Xie J, Silvermann D, Fusco D, Liang B, Yue L. TRPM7-Mediated Ca2+ Signals Confer Fibrogenesis in Human Atrial Fibrillation. Circulation Research. 2010; 106: 992-1003. (Featured on the cover of Circulation Research and was the first article by Editors’ pick)
Su LT, Chen HC, Gonzalez-Pagan O, Overton JD, Xie J, Yue L, Runnels LW. TRPM7 Activates m-Calpain by Stress-Dependent Stimulation of p38 MAPK and c-Jun N-Terminal Kinase. Journal of Molecular Biology. 2010; 396: 858-69
Du J, Xie J, Yue L. Modulation of TRPM2 by acidic pH and the underlying mechanisms for pH sensitivity. Journal of General Physiology. 2009; 134:471-488.
Heeringa S, Möller C, Du J, Yue L, Hinkes B1, Chernin G, Vlangos C, Hoyer P, Reiser J, and Hildebrandt F. A novel TRPC6 mutation in an early-onset family with FSGS strongly augments TRPC6 current amplitude. Plos One. 2009; 4:e7771.
Du J, Xie J, Yue L. Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proc Natl Acad Sci U S A. 2009; 107 (17) 1239-44.
Li M, Du J, Jiang J, Ratzan W, Su L-T, Runnels LW, Yue L. Molecular Determinants of Mg2+ and Ca2+ Permeability and pH Sensitivity in TRPM6 and TRPM7. J. Biol. Chem. 2007; 282(35):25817-25830.
Li M, Jiang J, Yue L. Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. Journal of General Physiology. 2006 May;127(5):525-37.
Su L, Agapito M, Li, Simpson W, Huttenlocher A, Habas R, Yue L, Runnel R. TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain. J Biol Chem. 2006 Apr 21;281(16):11260-70. Epub 2006 Jan 25.
Jiang J, Li M, Yue L. otentiation of TRPM7 inward currents by acidosis. Journal of General Physiology. 2005; 126 (2) 137-150.
*Runnels L, *Yue L, Clapham D. The TRP-Plik channel is inactivated by PIP2 hydrolysis. Nature Cell Biology.2002; 4(5):329-36. *Co-first author
Yue, L, Navarro B, Ren D, Clapham D. The cation selectivity filter of the bacterial sodium channel, NaChBac. Journal of General Physiology. 2002; 120 (6): 845-53.
Yue L, Peng J-B, Hediger M A, Clapham D.E. CaT1 Manifests the pore properties of the calcium release activated calcium channel. Nature. 2001; 410, 705-709. [see News and Views. Nature 2001 410:648-9].
*Ren D, *Navarro B, *Xu H, *Yue L, Shi Q, Clapham. A prokaryotic voltage-gated sodium channel. Science.2001 294(5550):2372-5. [see News and Views. Science 2001 294: 2306-2308]. *Co-first author.
Runnels L, Yue L, Clapham D. TRP-PLIK, a bifunctional protein with kinase and ion channel activities (Orginally published in Science Express as 10.1126/science. 1058519 on January 18, 2001). Science. 2001; 291(5506):1043-1047.
Yue L, Wang Z, Rindt H, Nattel S. Molecular evidence for a role of Shaw (Kv3) potassium channel subunits in potassium currents of dog atrium. Journal of Physiology. 2000; 527 (3): 467-478.
Nattel S, Li D, Yue L. “Basic mechanisms of atrial fibrillation-very new insights into very old ideas. Annual Review of Physiology. 2000; 62: 51-77.