Aistrup Lab

Dr. Aistrup’s research lab focuses on the basis of cardiac arrhythmias – irregular heart beat rates. Cardiac arrhythmias can occur in both the lower (ventricles) and upper (atria) of the heart, and while ventricular arrhythmias pose greater risk to life as they can lead to sudden cardiac death, atrial arrhythmias – i.e., atrial fibrillation – are the most common and while not immediately life-threatening can lead to stroke and heart failure. These arrhythmias can arise by several means consequent to heart disease (e.g., heart failure), myocardial infarctions or genetic anomalies resulting in ion channelopathies (e.g., long or short QT syndromes, Brugada syndrome) and/or cardiomyopathies (hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia). Dr. Aistrup’s main line of cardiac arrhythmia investigation is on how atypical calcium signaling in cardiomyocytes (heart muscle cells) contributes to arrhythmogenesis. Calcium is key in cardiac excitation-contraction (E-C) coupling – the cellular/molecular processes that underlie the heartbeat – and therefore any perturbation to calcium handling will affect heart function.

Moreover, as cardiac E-C coupling must be dynamic to meet the bodies changing demands, it is vitally modulated by multiple cell-signaling systems such as the autonomic (‘fight-or-flight’ and ‘rest-and-digest’ responses) and renin-angiotensin (blood pressure regulation) G-protein coupled receptor (GPCR) systems. His laboratory engages in the study of proarrhythmic abnormalities in both core E-C coupling and its modulatory systems, particularly under conditions of or leading to heart failure, and employs multiple methodologies to do so – i.e., cellular and tissue-level electrophysiology and live subcellular calcium imaging, as well as various immunological and molecular biological assays. While much of Dr. Aistrup’s research relies on utilizing both small and large animal models, upon joining the Masonic Medical Research Institute (MMRI), his laboratory has recently begun to incorporate human induced pluripotent stem cell-derived cardiomyocytes (h_iPSC-CMs) into his research, specifically to utilize them in the characterization and potential correction of genetic mutation-induced cardiac arrhythmias.

The overall goal of Dr. Aistrup’s research to elucidate and precisely characterize aberrant cellular/molecular underpinnings of cardiac arrhythmogenesis is to provide the basis for not only improved but patient-specific anti-arrhythmic therapies.

 

Principle Scientist/Assistant Professor, Masonic Medical Research Institute

Email : glais@mmri.edu, Phone : 315-624-7486

 

 

 

Dr. Aistrup began his research career working upon obtaining his PhD in biochemistry in the laboratories of Dr. Elias Michaelis, MD, PhD and Dr. Richard Schowen, PhD (Department of Chemistry) at the University of Kansas (title of dissertation: “Functional Reconstitution and Ion Channel Characterization of a NMDA/Glutamate Receptor in Planar Lipid Bilayers”). He went on to do a postdoctoral fellowship in the laboratory of Dr. Toshio Narahashi, PhD (Department of Molecular Pharmacology & Biological Chemistry) at Northwestern University Feinberg School of Medicine, where he investigated the alcohol action on GABAA and neuronal nicotinic acetylcholine receptor-ion channels. In 2000, Dr. Aistrup did another short-term postdoc in the laboratory of Richard Morrisett, PhD (Department of Pharmacology & Toxicology) at the University of Texas, Austin, studying amino acid synaptic transmission before returning to Northwestern University Feinberg School of Medicine in 2001 as a Research Assistant Professor in the Department of Molecular Pharmacology & Biological Chemistry. His initial research focus at Northwestern was on alcohol modulation of L-type calcium channels, which he quickly expanding to encompass alcohol effects on cardiac E-C coupling upon establishing a very productive collaboration with Dr. J. Andrew Wasserstrom, PhD (Department of Medicine, Division of Cardiology). Dr. Wasserstrom and Dr. Alan Kadish, MD (Department of Medicine, Division of Cardiology, Director of Clinical Electrophysiology) soon thereafter in 2004 recruited Dr. Aistrup to the Feinberg Cardiovascular Research Institute where he continued his collaborations with Dr. Wasserstrom and turning his research focus to the study of abnormal calcium release events during cardiac. In 2006, Dr. Aistrup established another productive collaboration with physician-scientist, Dr. Rishi Arora, investigating autonomic and oxidative stress modulation of atrial E-C coupling and electrophysiology in large-animal models of heart failure and atrial fibrillation. These research endeavors resulted in Dr. Aistrup being investigators on multiple NIH-funded grant projects, and allowed his rise to the rank of Research Associate Professor at the Feinberg Cardiovascular Institute. In latter part of 2016, was recruited to the Masonic Medical Research Institute as a Principle Research Scientist by Dr. Jonathan Cordeiro, PhD (interim Research Director).

Training

Dr. Aistrup earned a bachelor’s degree in Chemistry from Fort Hays State University, Hays KS, and obtained his PhD in Biology/Biochemistry under Dr. Elias Michaelis, MD, PhD and Dr. Richard Schowen, PhD at the University of Kansas, Lawrence KS. He did his postdoctoral training in molecular pharmacology and cellular electrophysiology with Toshio Narahashi, PhD at Northwestern University.

 

Why Masonic Medical Research Institute

A great opportunity to expand upon ongoing and develop new forward-looking biomedical research alongside newly recruited faculty and Director.

 

Affiliations

  • Heart Rhythm Society
  • American Physiological Society
  • Biophysical Society
  • Cardiac Electrophysiology Society
  • American Heart Association

 

Professional titles

  • Principle Scientist/Assistant Professor, Masonic Medical Research Institute (2016-present)
  • Research Associate Professor, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine (2014-2016)

 

Education

  • 1988 – BS, Chemistry Fort Hays State University
  • 1994 – PhD, Biochemistry University of Kansas

 

Honors and Awards

  • Royal Danish Academy of Science Annual Ion Channel Symposium Invited Speaker (2012, Copenhagen, Denmark)
  • Research Society on Alcoholism Annual Scientific Meeting Invited Symposium Speaker (1999, Santa Barbara, CA)
  • F32 Postdoctoral Fellowship Award (1996-1999) – “Ethanol on GABAA and Nicotinic Acetylcholine Receptor Intracellular Regulation”.

  1. Yoo, S, Aistrup, G, Shiferaw, Y, Ng, J, Mohler, PJ, Hund, TJ et al.. Oxidative stress creates a unique, CaMKII-mediated substrate for atrial fibrillation in heart failure. JCI Insight. 2018;3 (21):. doi: 10.1172/jci.insight.120728. PubMed PMID:30385719 PubMed Central PMC6238754.
  2. Shiferaw, Y, Aistrup, GL, Wasserstrom, JA. Synchronization of Triggered Waves in Atrial Tissue. Biophys. J. 2018;115 (6):1130-1141. doi: 10.1016/j.bpj.2018.08.015. PubMed PMID:30195941 PubMed Central PMC6139957.
  3. Calloe, K, Aistrup, GL, Di Diego, JM, Goodrow, RJ, Treat, JA, Cordeiro, JM et al.. Interventricular differences in sodium current and its potential role in Brugada syndrome. Physiol Rep. 2018;6 (14):e13787. doi: 10.14814/phy2.13787. PubMed PMID:30009404 PubMed Central PMC6046646.
  4. Singh, JK, Barsegyan, V, Bassi, N, Marszalec, W, Tai, S, Mothkur, S et al.. T-tubule remodeling and increased heterogeneity of calcium release during the progression to heart failure in intact rat ventricle. Physiol Rep. 2017;5 (24):. doi: 10.14814/phy2.13540. PubMed PMID:29279414 PubMed Central PMC5742703.
  5. Aistrup, GL, Arora, R, Grubb, S, Yoo, S, Toren, B, Kumar, M et al.. Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts. Cardiovasc. Res. 2017;113 (13):1688-1699. doi: 10.1093/cvr/cvx167. PubMed PMID:29016724 PubMed Central PMC5852523.
  6. Shiferaw, Y, Aistrup, GL, Wasserstrom, JA. Mechanism for Triggered Waves in Atrial Myocytes. Biophys. J. 2017;113 (3):656-670. doi: 10.1016/j.bpj.2017.06.026. PubMed PMID:28793220 PubMed Central PMC5549690.
  7. Barajas-Martinez, H, Goodrow, RJ, Hu, D, Patel, P, Desai, M, Panama, BK et al.. Biophysical and molecular comparison of sodium current in cells isolated from canine atria and pulmonary vein. Pflugers Arch. 2017;469 (5-6):703-712. doi: 10.1007/s00424-017-1956-4. PubMed PMID:28243733 .
  8. Arora, R, Aistrup, GL, Supple, S, Frank, C, Singh, J, Tai, S et al.. Regional distribution of T-tubule density in left and right atria in dogs. Heart Rhythm. 2017;14 (2):273-281. doi: 10.1016/j.hrthm.2016.09.022. PubMed PMID:27670628 PubMed Central PMC5484147.
  9. Kunamalla, A, Ng, J, Parini, V, Yoo, S, McGee, KA, Tomson, TT et al.. Constitutive Expression of a Dominant-Negative TGF-β Type II Receptor in the Posterior Left Atrium Leads to Beneficial Remodeling of Atrial Fibrillation Substrate. Circ. Res. 2016;119 (1):69-82. doi: 10.1161/CIRCRESAHA.115.307878. PubMed PMID:27217399 PubMed Central PMC4920729.
  10. Gordon, D, Goldberger, JJ, Arora, R, Aistrup, GL, Ng, J. Searching for "order" in atrial fibrillation using electrogram morphology recurrence plots. Comput. Biol. Med. 2015;65 :220-8. doi: 10.1016/j.compbiomed.2015.07.018. PubMed PMID:26255963 .
  11. Grubb, S, Aistrup, GL, Koivumäki, JT, Speerschneider, T, Gottlieb, LA, Mutsaers, NA et al.. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. Am. J. Physiol. Heart Circ. Physiol. 2015;309 (3):H481-9. doi: 10.1152/ajpheart.00166.2015. PubMed PMID:26055791 .
  12. Shah, SJ, Aistrup, GL, Gupta, DK, O'Toole, MJ, Nahhas, AF, Schuster, D et al.. Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure. Am. J. Physiol. Heart Circ. Physiol. 2014;306 (1):H88-100. doi: 10.1152/ajpheart.00642.2013. PubMed PMID:24186100 PubMed Central PMC3920157.
  13. Aistrup, GL, Gupta, DK, Kelly, JE, O'Toole, MJ, Nahhas, A, Chirayil, N et al.. Inhibition of the late sodium current slows t-tubule disruption during the progression of hypertensive heart disease in the rat. Am. J. Physiol. Heart Circ. Physiol. 2013;305 (7):H1068-79. doi: 10.1152/ajpheart.00401.2013. PubMed PMID:23873796 PubMed Central PMC5504390.
  14. Nahhas, AF, Kumar, MS, O'Toole, MJ, Aistrup, GL, Wasserstrom, JA. Can triggered arrhythmias arise from propagation of calcium waves between cardiac myocytes?. Front Biosci (Elite Ed). 2013;5 :893-9. . PubMed PMID:23747904 .
  15. Koduri, H, Ng, J, Cokic, I, Aistrup, GL, Gordon, D, Wasserstrom, JA et al.. Contribution of fibrosis and the autonomic nervous system to atrial fibrillation electrograms in heart failure. Circ Arrhythm Electrophysiol. 2012;5 (4):640-9. doi: 10.1161/CIRCEP.111.970095. PubMed PMID:22722658 PubMed Central PMC3607299.
  16. Shiferaw, Y, Aistrup, GL, Wasserstrom, JA. Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias. Cardiovasc. Res. 2012;95 (3):265-8. doi: 10.1093/cvr/cvs155. PubMed PMID:22542713 PubMed Central PMC3400355.
  17. Aistrup, GL, Balke, CW, Wasserstrom, JA. Arrhythmia triggers in heart failure: the smoking gun of [Ca2+]i dysregulation. Heart Rhythm. 2011;8 (11):1804-8. doi: 10.1016/j.hrthm.2011.06.012. PubMed PMID:21699870 .
  18. Aistrup, GL, Cokic, I, Ng, J, Gordon, D, Koduri, H, Browne, S et al.. Targeted nonviral gene-based inhibition of Gα(i/o)-mediated vagal signaling in the posterior left atrium decreases vagal-induced atrial fibrillation. Heart Rhythm. 2011;8 (11):1722-9. doi: 10.1016/j.hrthm.2011.06.018. PubMed PMID:21689540 PubMed Central PMC3570566.
  19. Ng, J, Villuendas, R, Cokic, I, Schliamser, JE, Gordon, D, Koduri, H et al.. Autonomic remodeling in the left atrium and pulmonary veins in heart failure: creation of a dynamic substrate for atrial fibrillation. Circ Arrhythm Electrophysiol. 2011;4 (3):388-96. doi: 10.1161/CIRCEP.110.959650. PubMed PMID:21421805 PubMed Central PMC3607326.
  20. Chen, W, Aistrup, G, Wasserstrom, JA, Shiferaw, Y. A mathematical model of spontaneous calcium release in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 2011;300 (5):H1794-805. doi: 10.1152/ajpheart.01121.2010. PubMed PMID:21357507 PubMed Central PMC3094092.
  21. Kapur, S, Aistrup, GL, Sharma, R, Kelly, JE, Arora, R, Zheng, J et al.. Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 2010;299 (6):H1843-53. doi: 10.1152/ajpheart.00623.2010. PubMed PMID:20889840 PubMed Central PMC3006292.
  22. Wasserstrom, JA, Shiferaw, Y, Chen, W, Ramakrishna, S, Patel, H, Kelly, JE et al.. Variability in timing of spontaneous calcium release in the intact rat heart is determined by the time course of sarcoplasmic reticulum calcium load. Circ. Res. 2010;107 (9):1117-26. doi: 10.1161/CIRCRESAHA.110.229294. PubMed PMID:20829511 PubMed Central PMC2967435.
  23. Guddati, AK, Otero, JJ, Kessler, E, Aistrup, G, Wasserstrom, JA, Han, X et al.. Embryonic stem cells overexpressing Pitx2c engraft in infarcted myocardium and improve cardiac function. Int Heart J. 2009;50 (6):783-799. . PubMed PMID:19952475 PubMed Central PMC3806488.
  24. Wasserstrom, JA, Sharma, R, Kapur, S, Kelly, JE, Kadish, AH, Balke, CW et al.. Multiple defects in intracellular calcium cycling in whole failing rat heart. Circ Heart Fail. 2009;2 (3):223-32. doi: 10.1161/CIRCHEARTFAILURE.108.811539. PubMed PMID:19808344 .
  25. Wasserstrom, JA, Sharma, R, O'Toole, MJ, Zheng, J, Kelly, JE, Shryock, J et al.. Ranolazine antagonizes the effects of increased late sodium current on intracellular calcium cycling in rat isolated intact heart. J. Pharmacol. Exp. Ther. 2009;331 (2):382-91. doi: 10.1124/jpet.109.156471. PubMed PMID:19675298 .
  26. Aistrup, GL, Villuendas, R, Ng, J, Gilchrist, A, Lynch, TW, Gordon, D et al.. Targeted G-protein inhibition as a novel approach to decrease vagal atrial fibrillation by selective parasympathetic attenuation. Cardiovasc. Res. 2009;83 (3):481-92. doi: 10.1093/cvr/cvp148. PubMed PMID:19457892 PubMed Central PMC2709464.
  27. Kapur, S, Wasserstrom, JA, Kelly, JE, Kadish, AH, Aistrup, GL. Acidosis and ischemia increase cellular Ca2+ transient alternans and repolarization alternans susceptibility in the intact rat heart. Am. J. Physiol. Heart Circ. Physiol. 2009;296 (5):H1491-512. doi: 10.1152/ajpheart.00539.2008. PubMed PMID:19286955 .
  28. Aistrup, GL, Shiferaw, Y, Kapur, S, Kadish, AH, Wasserstrom, JA. Mechanisms underlying the formation and dynamics of subcellular calcium alternans in the intact rat heart. Circ. Res. 2009;104 (5):639-49. doi: 10.1161/CIRCRESAHA.108.181909. PubMed PMID:19150887 .
  29. Wasserstrom, JA, Kapur, S, Jones, S, Faruque, T, Sharma, R, Kelly, JE et al.. Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences. Am. J. Physiol. Heart Circ. Physiol. 2008;295 (5):H1895-904. doi: 10.1152/ajpheart.00469.2008. PubMed PMID:18775850 PubMed Central PMC2614572.
  30. Cordeiro, JM, Malone, JE, Di Diego, JM, Scornik, FS, Aistrup, GL, Antzelevitch, C et al.. Cellular and subcellular alternans in the canine left ventricle. Am. J. Physiol. Heart Circ. Physiol. 2007;293 (6):H3506-16. doi: 10.1152/ajpheart.00757.2007. PubMed PMID:17906109 PubMed Central PMC2366895.
  31. Aistrup, GL, Kelly, JE, Kapur, S, Kowalczyk, M, Sysman-Wolpin, I, Kadish, AH et al.. Pacing-induced heterogeneities in intracellular Ca2+ signaling, cardiac alternans, and ventricular arrhythmias in intact rat heart. Circ. Res. 2006;99 (7):e65-73. doi: 10.1161/01.RES.0000244087.36230.bf. PubMed PMID:16960102 .
  32. Aistrup, GL, Kelly, JE, Piano, MR, Wasserstrom, JA. Biphasic changes in cardiac excitation-contraction coupling early in chronic alcohol exposure. Am. J. Physiol. Heart Circ. Physiol. 2006;291 (3):H1047-57. doi: 10.1152/ajpheart.00214.2006. PubMed PMID:16648190 .
  33. Wasserstrom, JA, Aistrup, GL. Digitalis: new actions for an old drug. Am. J. Physiol. Heart Circ. Physiol. 2005;289 (5):H1781-93. doi: 10.1152/ajpheart.00707.2004. PubMed PMID:16219807 .
  34. Nishio, M, Ruch, SW, Kelly, JE, Aistrup, GL, Sheehan, K, Wasserstrom, JA et al.. Ouabain increases sarcoplasmic reticulum calcium release in cardiac myocytes. J. Pharmacol. Exp. Ther. 2004;308 (3):1181-90. doi: 10.1124/jpet.103.060004. PubMed PMID:14634043 .
  35. Bian, JT, Yeh, JZ, Aistrup, GL, Narahashi, T, Moore, EJ. Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine. Eur. J. Pharmacol. 2002;453 (2-3):159-66. . PubMed PMID:12398899 .
  36. Zuo, Y, Aistrup, GL, Marszalec, W, Gillespie, A, Chavez-Noriega, LE, Yeh, JZ et al.. Dual action of n-alcohols on neuronal nicotinic acetylcholine receptors. Mol. Pharmacol. 2001;60 (4):700-11. . PubMed PMID:11562431 .
  37. Narahashi, T, Söderpalm, B, Ericson, M, Olausson, P, Engel, JA, Zhang, X et al.. Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers. Alcohol. Clin. Exp. Res. 2001;25 (5 Suppl ISBRA):152S-156S. . PubMed PMID:11391065 .
  38. Mori, T, Zhao, X, Zuo, Y, Aistrup, GL, Nishikawa, K, Marszalec, W et al.. Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons. Mol. Pharmacol. 2001;59 (4):732-43. . PubMed PMID:11259617 .
  39. Narahashi, T, Fenster, CP, Quick, MW, Lester, RA, Marszalec, W, Aistrup, GL et al.. Symposium overview: mechanism of action of nicotine on neuronal acetylcholine receptors, from molecule to behavior. Toxicol. Sci. 2000;57 (2):193-202. . PubMed PMID:11006350 .
  40. Mori, T, Aistrup, GL, Nishikawa, K, Marszalec, W, Yeh, JZ, Narahashi, T et al.. Basis of variable sensitivities of GABA(A) receptors to ethanol. Alcohol. Clin. Exp. Res. 2000;24 (7):965-71. . PubMed PMID:10923998 .
  41. Narahashi, T, Aistrup, GL, Marszalec, W, Nagata, K. Neuronal nicotinic acetylcholine receptors: a new target site of ethanol. Neurochem. Int. 1999;35 (2):131-41. . PubMed PMID:10405997 .
  42. Marszalec, W, Aistrup, GL, Narahashi, T. Ethanol-nicotine interactions at alpha-bungarotoxin-insensitive nicotinic acetylcholine receptors in rat cortical neurons. Alcohol. Clin. Exp. Res. 1999;23 (3):439-45. . PubMed PMID:10195816 .
  43. Narahashi, T, Aistrup, GL, Lindstrom, JM, Marszalec, W, Nagata, K, Wang, F et al.. Ion channel modulation as the basis for general anesthesia. Toxicol. Lett. 1998;100-101 :185-91. . PubMed PMID:10049141 .
  44. Aistrup, GL, Marszalec, W, Narahashi, T. Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons. Mol. Pharmacol. 1999;55 (1):39-49. . PubMed PMID:9882696 .
  45. Marszalec, W, Aistrup, GL, Narahashi, T. Ethanol modulation of excitatory and inhibitory synaptic interactions in cultured cortical neurons. Alcohol. Clin. Exp. Res. 1998;22 (7):1516-24. . PubMed PMID:9802537 .
  46. Nagata, K, Aistrup, GL, Huang, CS, Marszalec, W, Song, JH, Yeh, JZ et al.. Potent modulation of neuronal nicotinic acetylcholine receptor-channel by ethanol. Neurosci. Lett. 1996;217 (2-3):189-93. . PubMed PMID:8916104 .
  47. Aistrup, GL, Szentirmay, M, Kumar, KN, Babcock, KK, Schowen, RL, Michaelis, EK et al.. Ion channel properties of a protein complex with characteristics of a glutamate/N-methyl-D-aspartate receptor. FEBS Lett. 1996;394 (2):141-8. . PubMed PMID:8843152 .
  48. Nagata, K, Aistrup, GL, Song, JH, Narahashi, T. Subconductance-state currents generated by imidacloprid at the nicotinic acetylcholine receptor in PC 12 cells. Neuroreport. 1996;7 (5):1025-8. . PubMed PMID:8804044 .
  49. Michaelis, EK, Michaelis, ML, Kumar, KN, Tilakaratne, N, Joseph, DB, Johnson, PS et al.. Purification, reconstitution, and cloning of an NMDA receptor-ion channel complex from rat brain synaptic membranes: implications for neurobiological changes in alcoholism. Ann. N. Y. Acad. Sci. 1992;654 :7-18. . PubMed PMID:1378712 .
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