Professor
Department of Cell Biology

Education and Training

Ph.D., McGill University
Postdoctoral Fellow, Howard Hughes Medical Institute, Children’s Hospital, Harvard Medical School

Contact

Phone: 860-679-3869
Fax: 860-679-1426
Email: lyue@uchc.edu
Office: ARB G024

UConn Health
263 Farmington Avenue
Farmington, CT 06030

Curriculum Vitae

Research Interests

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:

1. TRP channels and calcium signaling mechanisms in cardiac fibrogenesis.
2. Gating mechanism and physiological functions of TRPM7 and TRPM6, the two channel-kinase proteins that exhibit both channel functions and protein kinase activities.
3. Gating mechanisms and potential roles of TRPM2

Selected Publications

Afzal J, Liu Y, Du W, Suhail Y, Zong P, Feng J, Ajeti V, Sayyad WA, Nikolaus J, Yankova M, Deymier AC, Yue L, Kshitiz. Cardiac ultrastructure inspired matrix induces advanced metabolic and functional maturation of differentiated human cardiomyocytes. Cell Rep. 2022 Jul 26;40(4):111146. doi: 10.1016/j.celrep.2022.111146. PubMed PMID: 35905711.

Phoenix KN, Yue Z, Yue L, Cronin CG, Liang BT, Hoeppner LH, Claffey KP. PLC (Phospholipase C) β2 Promotes VEGF (Vascular Endothelial Growth Factor)-Induced Vascular Permeability. Arterioscler Thromb Vasc Biol. 2022 Jul 21;:101161ATVBAHA122317645. doi: 10.1161/ATVBAHA.122.317645. [Epub ahead of print] PubMed PMID: 35861069.

Zong P, Feng J, Yue Z, Li Y, Wu G, Sun B, He Y, Miller B, Yu AS, Su Z, Xie J, Mori Y, Hao B, Yue L. Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury. Neuron. 2022 Jun 15;110(12):1944-1958.e8. doi: 10.1016/j.neuron.2022.03.021. Epub 2022 Apr 13. PubMed PMID: 35421327; PubMed Central PMCID: PMC9233078.

Zong P, Feng J, Yue Z, Yu AS, Vacher J, Jellison ER, Miller B, Mori Y, Yue L. TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages. Nat Cardiovasc Res. 2022 Apr;1(4):344-360. doi: 10.1038/s44161-022-00027-7. Epub 2022 Mar 28. PubMed PMID: 35445217; PubMed Central PMCID: PMC9015693.

Zong P, Lin Q, Feng J, Yue L. A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death. Cells. 2022 Jan 31;11(3). doi: 10.3390/cells11030491. Review. PubMed PMID: 35159300; PubMed Central PMCID: PMC8834171.

Bai Z, Feng J, Franken GAC, Al’Saadi N, Cai N, Yu AS, Lou L, Komiya Y, Hoenderop JGJ, de Baaij JHF, Yue L, Runnels LW. CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. PLoS Biol. 2021 Dec;19(12):e3001496. doi: 10.1371/journal.pbio.3001496. eCollection 2021 Dec. PubMed PMID: 34928937; PubMed Central PMCID: PMC8726484.

Yue L, Xu H. TRP channels in health and disease at a glance. J Cell Sci. 2021 Jul 1;134(13). doi: 10.1242/jcs.258372. Epub 2021 Jul 13. PubMed PMID: 34254641; PubMed Central PMCID: PMC8358089.

Curry EJ, Le TT, Das R, Ke K, Santorella EM, Paul D, Chorsi MT, Tran KTM, Baroody J, Borges ER, Ko B, Golabchi A, Xin X, Rowe D, Yue L, Feng J, Morales-Acosta MD, Wu Q, Chen IP, Cui XT, Pachter J, Nguyen TD. Biodegradable nanofiber-based piezoelectric transducer. Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):214-220. doi: 10.1073/pnas.1910343117. Epub 2019 Dec 23. PubMed PMID: 31871178; PubMed Central PMCID: PMC6955346.

Alexander SPH, Mathie A, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Br J Pharmacol. 2019 Dec;176 Suppl 1:S142-S228. doi: 10.1111/bph.14749. PubMed PMID: 31710715; PubMed Central PMCID: PMC6844578.

Feng J, Armillei MK, Yu AS, Liang BT, Runnels LW, Yue L. Ca²⁺ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases. J Cardiovasc Dev Dis. 2019 Sep 23;6(4). doi: 10.3390/jcdd6040034. Review. PubMed PMID: 31547577; PubMed Central PMCID: PMC6956282.

Hiraishi K, Kurahara LH, Sumiyoshi M, Hu YP, Koga K, Onitsuka M, Kojima D, Yue L, Takedatsu H, Jian YW, Inoue R. Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel. World J Gastroenterol. 2018 Sep 21;24(35):4036-4053. doi: 10.3748/wjg.v24.i35.4036. PubMed PMID: 30254408; PubMed Central PMCID: PMC6148431.

Yu AS, Yue Z, Feng J, Yue L. Regulation of Orai/STIM Channels by pH. 2018;. doi: 10.1201/9781315152592-9. Review. PubMed PMID: 30299649.

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.