Laboratory of Kathrin Banach, PhD

Our research focuses on the cellular mechanism of atrial fibrillation (AF), which is the most common cardiac arrhythmia in clinical practice that can precipitate heart failure, stroke and even death. On the cellular level, AF is induced by spontaneous arrhythmic trigger activity outside the sinus node and/or changes in atrial excitation spread that facilitate re-entry of excitation due to altered cell-cell communication or tissue fibrosis. The mechanisms that induce AF are not entirely understood and, currently, there is no effective pharmacological therapy.

Our work

In our previous work, we have quantified the mechanisms by which cardiomyocytes develop spontaneous rhythmic or arrhythmic activity under physiological and pathophysiological conditions. In this context, we quantified changes in excitability and excitation spread due to increased fibrosis, taking into account enhanced intercellular coupling or paracrine signaling between myocytes and non-myocytes.

In an ongoing project, we have identified that the expression of the p21-activated kinase (Pak1) is decreased in the etiology of AF in patients and animal models of AF and that attenuation of atrial Pak1 activity increases atrial arrhythmic activity. The current aims of the laboratory are to determine the molecular mechanisms for the following:

  • Pak1 is reduced in patients with AF.
  • Reduced Pak1 increases the propensity of AF due to increased trigger activity and tissue remodeling.
  • Pak1 is a negative regulator of cellular production of reactive oxygen species.
  • Stabilization of Pak1 expression can attenuate AF.

The overall goal is to understand the role of Pak1 in atrial function and to use this understanding to develop a pharmacological approach for the treatment AF.

In a new collaborative project between basic researchers at Rush (Drs. Banach and Blatter) and clinical faculty (Drs. Feinstein and Okwuosa, Department of Cardiology), an animal model was developed to determine the molecular mechanism of chemotherapy-induced cardiotoxicity and to explore mechanisms of cardiac-specific drug delivery for cardioprotection.

Technology and methods

  • Patch clamp technique; single and double whole cell voltage clamp and current clamp;
  • Confocal imaging of intracellular Calcium and Sodium concentration, and production of reactive oxygen species
  • Multi-electrode array recordings for quantification of excitation spread and homo-/heterogeneity of tissue excitability
  • whole heart functional recordings using echocardiography, ECG and transesophageal pacing to determine AF inducibility (in vivo) and in the Langendorff configuration using multi-electrode arrays to quantify tissue excitability and excitation spread

Publications

Select works

  • Kapur N, Mignery G, and Banach K. (2006.) “Cell Cycle Dependent Calcium Oscillations in Mouse Embryonic Stem Cells.” Am J Physiol Cell Physiol. 292(4):C1510-C1518.
  • Shang LL, Pfahnl AE, Sanyal S, Jiao Z, Allen J, Banach K, Fahrenbach J, Weiss D, Taylor WR, Zafari AM & Dudley SC, Jr. (2007.) “Human Heart Failure Is Associated With Abnormal C-Terminal Splicing Variants in the Cardiac Sodium Channel.” Circ Res.101(11):1146-54
  • Kapur N and Banach K. (2007.) “IP3 Mediated Ca Signaling Drives Pacemaker Activity in Early ES Cell Derived Cardiomyocytes.” J. Physiol. 58: 1113–1127. PMC2170837
  • Fahrenbach J, Mejia-Alvarez R and Banach K. (2007.) “The Relevance of Non-Excitable Cells for Cardiac Pacemaker Function.” J Physiol. 585(Pt 2):565-78. PMC2375482
  • Fahrenbach JP, Ai X, and Banach K. (2008.) “Decreased Intercellular Coupling Improves the Function of Cardiac Pacemakers Derived from Mouse Embryonic Stem Cells.” J Mol Cell Cardiol. 45, 642-649. PMC2598737
  • Rinne A, Banach K, and Blatter LA. (2009.) “Regulation of Nuclear Factor of Activated T Cells (NFAT) in Vascular Endothelial Cells.” J Mol Cell Cardiol 47, 400-410. PMCID: PMC2779755
  • Grajales L, Garcia J, Banach K, and Geenen DL. (2010.) “Delayed Enrichment of Mesenchymal Cells Promotes Cardiac Lineage and Calcium Transient Development.” J Mol Cell Cardiol. 48, 735-745. PMCID: PMC2837799
  • Rinne A, Kapur N, Molkentin JD, Pogwizd SM, Bers DM, Banach K, and Blatter LA. (2010.) “Isoform- and Tissue-Specific Regulation of the Ca2+-Sensitive Transcription Factor NFAT in Cardiac Myocytes and in Heart Failure.” Am J Physiol Heart Circ Physiol 298, H2001-2009. PMCID: PMC2886636
  • DeSantiago, JD, Bare D, Semenov I, Minshall RD, Geenen DL, Wolska BM, and Banach K (2012.) “Excitation-Contraction Coupling in Ventricular Myocytes is Enhanced by Paracrine Signaling from Mesenchymal Stem Cells.” J Mol Cell Cardiol. 52, 1249-1256. PMCID: PMC3570146
  • Mureli S, Gans CP, Bare DJ, Geenen DL, Kumar NM, and Banach K (2013.) “Mesenchymal Stem Cells Improve Cardiac Conduction by Up-Regulation of Connexin 43 Through Paracrine Signaling.” Am J Physiol Heart Circ Physiol. 304:H600-H609(Podcast Featured Article) PMCID: PMC3566487
  • DeSantiago J, Bare DJ and Banach K. (2013.) “Protection from Ischemia Reperfusion Injury by Mitochondrial IK,ATP Activation Through Mesenchymal Stem Cell Derived Paracrine Factors.” Stem Cell and Development. 22: 2497-2507; PMCID: PMC3760058
  • DeSantiago J, Bare DJ, Ke Y, Sheehan KA, Solaro RJ and Banach K (2013.) “Functional Integrity of the T-Tubular System in Cardiomyocytes Depends on p21-Activated Kinase 1.” J. Mol. Cell. Cardiol. 60:121–128. PMCID: PMC3679655
  • Taglieri DM, Johnson KR, Burmeister BT, Monasky MM, Spindler MJ, Desantiago J, Banach K, Conklin BR, Carnegie GK. (2014.) “The C-Terminus of the Long AKAP13 Isoform (AKAP-Lbc) Is Critical for Development of Compensatory Cardiac Hypertrophy. J. Mol. Cell. Cardiol. 66: 27–40.
  • DeSantiago J, Bare DJ, Xiao L, Ke Y, Solaro RJ, Banach K. (2014.) “p21-Activated Kinase1 (Pak1) Is a Negative Regulator of NADPH-Oxidase 2 in Ventricular Myocytes. J. Mol. Cell. Cardiol. 67: 77-85. PMCID: PMC3930036
  • Kapoor N, Maxwell JT, Mignery GA, Will D, Blatter LA, Banach K. (2014.) “Spatially Defined InsP3-Mediated Signaling in Embryonic Stem Cell-Derived Cardiomyocytes.” PLoS One 9: e83715. PMCID: PMC3883750

Additional research

A more complete listing of Banach’s published work can be found on PubMed.

Funding

Current grants

  • AHA Grant in Aid: "Role of p21-Activated Kinase in Atrial Fibrillation," 07/2015 – 06/2017. Role: Principal investigator
  • NIH 1R01HL128330:" Role of p21-Activated Kinase (Pak1) in Atrial Fibrillation,” 04/2016 – 03/2021.

Past grants

  • AHA Scientist Development Grant:"Embryonic Stem Cell Derived Biological Pacemaker for the Heart," 07/2003-06/2006.
  • NIH 1R01HL089617: "Embryonic Stem Cell Derived Biological Pacemaker for the Heart," 07/2007 – 06/2013. Role: Principal investigator
  • NIH 3R01HL089617-03S: “Embryonic Stem Cell Derived Biological Pacemaker for the Heart," 07/2009 – 06/2011. Role: Principal investigator

Our team

Banach’s laboratory has trained two medical students, two master-level students, two PhD students, three post-doctoral students and cardiology fellows.

  • Jaime DeSantiago, MD, PhD, instructor
  • Megan Covington, Medical Student

Opportunities

Contact

Kathrin Banach, PhD
Assistant Professor
Track Director Cardiovascular and Respiratory Biology

Rush University
Division of Cardiology, Department of Internal Medicine
Jelke Building
1750 W. Harrison St., Room 1419
Chicago, IL 60612

Phone: (312) 563-3553