Kass Lab
Location and Contact Information
- Office Phone 212-305-8701
- Lab Phone 212-305-8696
Principal Investigator
Research Overview
Dr. Kass' laboratory has focused on understanding the molecular physiology and pharmacology of congenital arrhythmias. These arrhythmias are caused by inherited mutations in genes coding for ion channels and/or ion channel related proteins expressed in the heart. This work has contributed to an understanding of gene-specific risk factors caused by mutation-induced changes in heart ion channel activity, and to the development of a mutation-specific approach to manage these disorders. The mutation-specific therapeutic strategy, verified in genotyped patients, has established the principle that two variants of the same genetic disorder require dramatically different therapeutic strategies for disease management based on biophysical properties of specific genetic lesions. This approach has evolved from close collaborations with clinical colleagues in which information is shared from clinic to basic laboratory and back to clinic.
Additional studies are aimed at unraveling the structural basis of mutation-induced, and potentially lethal, disease phenotypes using approaches such as voltage-clamp fluorometry to directly measure movement of gating machinery in the ion channel of interest as well as biochemical methods of directly probing structures of region of ion channels that are hotspots for disease-causing mutations and the use of computer-based modeling to understand both structure and functional consequences of these mutations.
Work has additionally more recently focused on potassium ion channel mutations that underlie a form of heritable pulmonary arterial hypertension. This work has provided information not only of novel pathways that contribute to this disease, but also to new routes of therapeutic management of this disorder. The goal of this approach is to unmask new and specific targets for the development of anti-arrhythmic drugs.
Currently, work in the laboratory focused on the study of mechanisms underlying heritable arrhythmias in the context of complex genetic backgrounds has studied the cellular electrophysiology of cardiomyocytes differentiated from inducible pluripotent stem cells derived from family members of patients harboring disease-causing mutations. This approach has offered opportunities to screen drugs for effective disease management when multiple genes may be involved in the disease phenotype.
About Dr. Kass
Dr. Kass has directed NIH and/or NSF sponsored research for forty-two years that has contributed to our understanding of the fundamental cellular and molecular basis of cardiac electrical activity through a multidisciplinary approach bridging basic biophysical and clinical science. Contributions from this work include the cellular basis of calcium-dependent arrhythmogenic activity in the heart, basic mechanisms of action of calcium channel blocking drugs, and the molecular events underlying the control of the duration of electrical events in the heart during sympathetic nerve stimulation.
Lab Members
Select Publications
Li Y, Hof T, Baldwin TA, Chen L, Kass RS, and Dessauer CW. Regulation of IKs Potassium Current by Isoproterenol in Adult Cardiomyocytes Requires Type 9 Adenylyl Cyclase. Cells. 2019;8(9).
Shandell MA, Quejada JR, Yazawa M, Cornish VW, and Kass RS. Detection of Nav1.5 Conformational Change in Mammalian Cells Using the Noncanonical Amino Acid ANAP. Biophys J. 2019;117(7):1352-63.
Bohnen MS, Ma L, Zhu N, Qi H, McClenaghan C, Gonzaga-Jauregui C, et al. Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension. Circ Genom Precis Med. 2018;11(10):e002087.
Peng G, Barro-Soria R, Sampson KJ, Larsson HP, and Kass RS. Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations. Sci Rep. 2017;7:45911.
Barro-Soria R, Ramentol R, Liin SI, Perez ME, Kass RS, and Larsson HP. KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions. Proc Natl Acad Sci U S A. 2017;114(35):E7367-E76.
Bohnen MS, Roman-Campos D, Terrenoire C, Jnani J, Sampson KJ, Chung WK, et al. The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery. J Am Heart Assoc. 2017;6(9).
Bohnen MS, Peng G, Robey SH, Terrenoire C, Iyer V, Sampson KJ, et al. Molecular Pathophysiology of Congenital Long QT Syndrome. Physiol Rev. 2017;97(1):89-134.
Eng G, Lee BW, Protas L, Gagliardi M, Brown K, Kass RS, et al. Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes. Nat Commun. 2016;7:10312.
Lorberbaum T, Sampson KJ, Chang JB, Iyer V, Woosley RL, Kass RS, et al. Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation. J Am Coll Cardiol. 2016;68(16):1756-64.
Chen L, Sampson KJ, and Kass RS. Cardiac Delayed Rectifier Potassium Channels in Health and Disease. Card Electrophysiol Clin. 2016;8(2):307-22.
Lorberbaum T, Sampson KJ, Woosley RL, Kass RS, and Tatonetti NP. An Integrative Data Science Pipeline to Identify Novel Drug Interactions that Prolong the QT Interval. Drug Saf. 2016;39(5):433-41.
Iyer V, Roman-Campos D, Sampson KJ, Kang G, Fishman GI, and Kass RS. Purkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3. Sci Rep. 2015;5:13287.
Iyer V, Sampson KJ, and Kass RS. Modeling tissue- and mutation- specific electrophysiological effects in the long QT syndrome: role of the Purkinje fiber. PLoS One. 2014;9(6):e97720.
Barro-Soria R, Rebolledo S, Liin SI, Perez ME, Sampson KJ, Kass RS, et al. KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps. Nat Commun. 2014;5:3750.
Dvir M, Strulovich R, Sachyani D, Ben-Tal Cohen I, Haitin Y, Dessauer C, et al. Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP(2). J Cell Sci. 2014;127(Pt 18):3943-55.
Terrenoire C, Wang K, Tung KW, Chung WK, Pass RH, Lu JT, et al. Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics. J Gen Physiol. 2013;141(1):61-72.
Moreno JD, Yang PC, Bankston JR, Grandi E, Bers DM, Kass RS, et al. Ranolazine for congenital and acquired late INa-linked arrhythmias: in silico pharmacological screening. Circ Res. 2013;113(7):e50-61.