Laboratory of Xun Ai, MD
Our research is focused on understanding the mechanisms of cardiac arrhythmias, especially atrial fibrillation, or AF, in the aging heart per se and in the aged heart with co-existing cardiovascular diseases.
Our work
We recently discovered that c-jun N terminal kinase, or JNK, plays a critical role in atrial gap junctional remodeling and atrial arrhythmia development in aged atria. With grant support from the NIH and American Heart Association, we are conducting exciting research that will substantially increase our understanding of JNK signaling as a critical contributor to arrhythmia development in aged atria. Our current research focus will help us to achieve our long-term goal to further understand the relationship between aging and co-existing cardiovascular disease in the development of AF and, ultimately, to develop novel and effective therapeutic strategies for AF prevention and treatment in the elderly.
In addition to our expertise on molecular biochemistry techniques, we have established many leading-edge electrophysiological techniques, including the following:
- Optical mapping calcium transients, or Ca, and action potentials, or AP, simultaneously in intact hearts
- Using two-photon microscopy to obtain super-resolution images of Ca / AP and define myocardial and interstitial matrix structure in the same intact hearts,
- In vivo/ex vivo cardiac arrhythmia induction.
- Measuring intercellular resistivity using a novel four-electrode microimpedance technique in intact hearts.
Select publications
Ai X, Yan J, Carrillo E, Ding W. The Stress-Response MAP Kinase Signaling in Cardiac Arrhythmias. Rev Physiol Biochem Pharmacol. 2016;172:77-100. PMID:27848025
Yan J, Thomson JK, Zhao W, Fast VG, Ye T, Ai X. Voltage and calcium dual channel optical mapping of cultured HL-1 atrial myocyte monolayer. J Vis Exp. 2015 Mar 23;(97). doi: 10.3791/52542. PMID:25867896
Zhang Y, Wu S, Ma J, Xia Y, Ai X, Sun J. Bacterial protein AvrA stabilizes intestinal epithelial tight junctions via blockage of the C-Jun N-terminal kinase pathway. Tissue Barriers. 2015 Apr 3;3(1-2):e972849. doi: 10.4161/21688362.2014.972849. PMID:25838979
Ai X. SR calcium handling dysfunction, stress-response signaling pathways, and atrial fibrillation. Front Physiol. 2015 Feb 19;6:46. doi: 10.3389/fphys.2015.00046. Review. PMID:25745402
Yang X, Wang T, Lin X, Yue X, Wang Q, Wang G, Fu Q, Ai X, Chiang DY, Miyake CY, Wehrens XH, Chang J. Genetic deletion of Rnd3/RhoE results in mouse heart calcium leakage through upregulation of protein kinase A signaling. Circ Res. 2015 Jan 2;116(1):e1-e10. doi: 10.1161/CIRCRESAHA.116.304940. PMID:25348166
Gemel J, Levy AE, Simon AR, Bennett KB, Ai X, Akhter S, Beyer EC. Connexin40 abnormalities and atrial fibrillation in the human heart. J Mol Cell Cardiol. 2014 Nov;76:159-68. doi: 10.1016/j.yjmcc.2014.08.021. PMID:25200600
Yan J, Thomson JK, Wu X, Zhao W, Pollard AE, Ai X. Novel methods of automated quantification of gap junction distribution and interstitial collagen quantity from animal and human atrial tissue sections. PLoS One. 2014 Aug 8;9(8):e104357. doi: 10.1371/journal.pone.0104357. PMID:25105669
Wang Y, Yang Y, Ai X. Heart failure. ScientificWorldJournal. 2014 Feb 12;2014:730651. doi: 10.1155/2014/730651. PMID:24693244
Wang Y, Du Y, Ai X. Cardiac Electrophysiology: A Challenging and Fast Progressing Field. The Scientific World Journal 2013, Volume 2013. Article ID 909746
Yan J, Kong W, Zhang Q, Beyer EC, Walcott G, Fast VG, Ai X. c-Jun N-terminal kinase activation contributes to reduced Cx43 and atrial arrhythmia development in the aged rabbit left atria. Cardiovascular Res 2013, 97(3):589-97. PMID:23241357
Zhu Y, Ai X, Oster RA, Bers DM, Pogwizd SM. Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic Stimulation in rabbits. Pflugers Arch 2012, 465(6)805-18. PMID:23242028
Respress JL, van Oort RJ, Li N, Rolim N, Dixit S, Voigt N, Lawrence WS, Skapura DG, Wisloff U, Wieland T, Ai X, Pogwizd SM, Dobrev D, Wehrens XHT. Role of RyR2 Phosphorylation at S2814 during Heart Failure Progression. Circ Res 2012, 110(11):1474-83. PMID:22511749
Ai X, Jiang A, Ke Y, Solaro JR, Pogwizd SM. Enhanced expression of p21-activated kinases in an arrhythmogenic rabbit model of heart failure contributes to dephosphorylation of connexin 43. Cardiovasc Res, 2011, 92(1):106-14. PMID:21727092
Ai X (Corresponding Author), Zhao W, Pogwizd SM. Connexin 43 knockdown or overexpression modulates cell coupling in control and failing rabbit left ventricular myocytes. Cardiovasc Res 2010 Mar 1;85(4):751-62. PMID:19880431
DeSantiago J, Ai X, Islam M, Acuna G, Ziolo MT, Bers DM, Pogwizd SM. Arrhythmogenic effects of b2-adrenergic stimulation in the failing heart are due to enhanced SR Ca load. Circ Res 2008;102:1389-97. PMID:18467626
Fahrenbach J, Ai X, Banach K. Decreased intercellular coupling improves the function of cardiac pacemakers derived from mouse embryonic stem cells. J Mole Cell Cardiol 2008;45(5):642-9. PMID:18817780
Additional publications
A more complete listing of Ai’s published work can be found on PubMed.
Opportunities
Funding
Current grants
- NIH R01-HL146744-01 “Heart-platelet crosstalk: JNK, AF, and thrombogenesis” 05/15/19-02/28/23. Role: PI
- NIH R01-AA024769-01A1: “The Stress Response Kinase JNK and Alcohol Evoked Atrial Fibrillation.” 04/15/17-03/31/22. Role: PI
- NIH R01: Research minority supplemental grant affiliated to the parent grant “The Stress Response Kinase JNK and Alcohol Evoked Atrial Fibrillation.” 04/01/18-08/31/20. Role: PI
- NIH R01-HL062426-17: “Integrated Mechanisms of Cardiac Maladaptation.” 06/01/16-05/31/21. PI: Dr. Solaro. Role: Core Leader
- NIH R01-HL113640-04: “JNK Suppression of Connexin43 Enhances Atrial Fibrillation in Aged Atria.” 07/03/12-07/31/18. Role: PI
Our team
Xun Ai, MD, professor
Dan Bare, PhD, instructor
Jasson Barrios, research assistant
Elena Carrillo, research assistant
Jaime DeSantiago, MD, PhD, instructor
Jiajie Yan, PhD, postdoctoral fellow
Mei Yang, research assistant
Weiwei Zhao, BA, research assistant
Contact
Xun Ai, MD
Professor
Rush University
Department of Physiology & Biophysics
Jelke Building
1750 W. Harrison St., Room 1255
Chicago, IL 60612
Phone: (312) 563-1128
Fax: (312) 942-8711
Email: xun_ai@rush.edu