Wanda Krassowska Neu
Biomedical Engineering
Professor Emeritus of Biomedical Engineering
Research Themes
Bioelectric Engineering, Computational Modeling of Biological Systems, Drug & Gene Delivery, Neural Engineering
Research Interests
Electroporation-mediated drug delivery and gene therapy; Control of cardiac arrhythmias using nonlinear dynamics
Bio
Electroporation-Mediated Drug and Gene Delivery
Electroporation refers to the creation of small (1-40 nm) pores in the lipid bilayer of the membrane in response to large electric shocks. Electroporation occurs as an undesirable side effect in accidental contacts with high voltage wires or when defibrillation shocks are applied to the heart to prevent sudden cardiac death. However, electroporation has also important applications in biotechnology, as pores allow the introduction of drugs and DNA into cells. Still, this technique is largely empirical and the results are often variable and difficult to control. Our research in this area concentrates on the development of a model of electroporation that would allow theoretical investigation of the creation of pores during the shock, the flow of ions, drugs, and DNA through pores, and the resulting changes in intracellular concentrations.
Nonlinear Dynamics Approach to Cardiac Arrhythmias
Cardiac arrhythmias, serious and potentially fatal diseases, can only rarely be successfully controlled with medication. The only available treatment is defibrillation, the delivery of a large electric shock. Such shocks often have serious side effects. Our research investigates the feasibility of alternative treatments for cardiac tachyarrhythmias that instead of large shocks use an appropriately timed train of small pulses. The approach is based on the feedback protocols that have been developed to control the dynamics of complex nonlinear systems and involves animal experiments, mathematical modeling, and computer simulations. These studies allow us to gain a better insight into the dynamics of cardiac rhythm and to assess the feasibility of bringing an episode of arrhythmia under control, terminate it, or even inhibit its occurrence.
Education
- M.S. Warsaw University of Technology (Poland), 1978
- Ph.D. Duke University, 1987
Positions
- Professor Emeritus of Biomedical Engineering
- Bass Fellow
Awards, Honors, and Distinctions
- Klein Family Distinguished Teaching Award. Pratt School of Engineering. 2019
- Bass Society Fellow. Duke University. 2013
- Springer Visiting Professor in Mechanical Engineering. University of California at Berkeley. 2009
- Klein Family Distinguished Teaching Award. Pratt School of Engineering. 2008
Publications
- Idriss SF, Krassowska Neu W, Varadarajan V, Antonijevic T, Gilani SS, Starobin JM. Feasibility of non-invasive determination of the stability of propagation reserve in patients. Computing in Cardiology. 2012 Dec 1;39:353u20136.
- Cranford JP, Kim BJ, Neu WK. Asymptotic model of electrical stimulation of nerve fibers. Medical & biological engineering & computing. 2012 Mar;50(3):243u201351.
- Neu WK, Neu JC. Theory of electroporation. 2009 Dec 1;133u201361.
- Dobrovolny HM, Berger CM, Brown NH, Neu WK, Gauthier DJ. Spatial heterogeneity of restitution properties and the onset of alternans. Conference proceedingsu202f: . Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference. 2009 Dec 1;4186u20139.
- Dobrovolny HM, Berger CM, Brown NH, Neu WK, Gauthier DJ. Spatial heterogeneity of restitution properties and the onset of alternans. Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual International Conference. 2009 Jan;2009:4186u20139.
- Guo L, Neu JC, Cranford JP, Krassowska Neu W. Activating function of needle electrodes in anisotropic tissue. Med Biol Eng Comput. 2009;47:1001u201311.
- Variability of action potential duration in pharmacologically induced long QT syndrome type 1. Conference proceedingsu202f: . Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference. 2009 Jan 1;4520u20132.
- Ring CL, Idriss SF, Neu WK. Variability of action potential duration in pharmacologically induced long QT syndrome type 1. Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:4520u20132.
- Dobrovolny HM, Berger CM, Brown NH, Neu WK, Gauthier DJ. Spatial heterogeneity of restitution properties and the onset of alternans. Conference proceedingsu202f: . Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference. 2009;2009:4186u20139.
- Zhao X, Schaeffer DG, Berger CM, Krassowska W, Gauthier DJ. `Cardiac alternans arising from an unfolded border-collision bifurcation. J Comput Nonlinear Dynam. 2008 Oct;3:041004.
- Zhao X, Schaeffer DG, Berger CM, Krassowska W, Gauthier DJ. Cardiac alternans arising from an unfolded border-collision bifurcation. 2007 Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, DETC2007. 2008 Jan 1;5 PART A:223u201332.
- Berger CM, Zhao X, Schaeffer DG, Dobrovolny HM, Krassowska W, Gauthier DJ. Period-doubling bifurcation to alternans in paced cardiac tissue: crossover from smooth to border-collision characteristics. Physical review letters. 2007 Aug 3;99(5):058101.
- Berger CM, Zhao X, Schaeffer DG, Dobrovolny HM, Krassowska W, Gauthier DJ. Period-doubling bifurcation to alternans in paced cardiac tissue: crossover from smooth to border-collision characteristics. Physical review letters. 2007 Aug;99(5):058101.
- Pitruzzello AM, Krassowska W, Idriss SF. Spatial heterogeneity of the restitution portrait in rabbit epicardium. Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1568u201378.
- Schaeffer DG, Cain JW, Gauthier DJ, Kalb SS, Oliver RA, Tolkacheva EG, et al. An ionically based mapping model with memory for cardiac restitution. Bulletin of mathematical biology. 2007 Feb;69(2):459u201382.
- Zhao X, Schaeffer DG, Krassowska W, Gauthier DJ. A model-independent technique for eigenvalue identification and its application in predicting cardiac alternans. ASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE). 2007 Jan 1;2:301u20132.
- Krassowska W, Filev PD. Modeling electroporation in a single cell. Biophysical journal. 2007 Jan;92(2):404u201317.
- Bell J, Rouze N, Krassowska W, Idriss S. The Electrocardiogram Restitution Portrait Quantifying Dynamical Electrical Instability in Young Myocardium. Comput Cardiol. 2007;34:789u201392.
- Cranford JP, Zhao X, Krassowska W. Guidelines for controlling pore radii from nonlinear analysis of a two-dimensional model of electroporation. ASME International Mechanical Engineering Congress and Exposition, Proceedings (IMECE). 2007 Jan 1;2:307u20138.
- Neu JC, Krassowska W. Singular perturbation analysis of the pore creation transient. Physical review E, Statistical, nonlinear, and soft matter physics. 2006 Sep;74(3 Pt 1):031917.
- Oliver RA, Krassowska W. Reproducing cardiac restitution properties using the Fenton-Karma membrane model. Annals of biomedical engineering. 2005 Jul;33(7):907u201311.
- Kalb SS, Tolkacheva EG, Schaeffer DG, Gauthier DJ, Krassowska W. Restitution in mapping models with an arbitrary amount of memory. Chaos (Woodbury, NY). 2005 Jun;15(2):23701.
- Oliver RA, Henriquez CS, Krassowska W. Bistability and correlation with arrhythmogenesis in a model of the right atrium. Annals of biomedical engineering. 2005 May;33(5):577u201389.
- Kalb SS, Dobrovolny HM, Tolkacheva EG, Idriss SF, Krassowska W, Gauthier DJ. The restitution portrait: a new method for investigating rate-dependent restitution. J Cardiovasc Electrophysiol. 2004 Jun;15(6):698u2013709.
- Smith KC, Neu JC, Krassowska W. Model of creation and evolution of stable electropores for DNA delivery. Biophysical journal. 2004 May;86(5):2813u201326.
- Dev SB, Dhar D, Krassowska W. Electric field of a six-needle array electrode used in drug and DNA delivery in vivo: analytical versus numerical solution. IEEE transactions on bio-medical engineering. 2003 Nov;50(11):1296u2013300.
- Neu JC, Smith KC, Krassowska W. Electrical energy required to form large conducting pores. Bioelectrochemistry (Amsterdam, Netherlands). 2003 Aug;60(1u20132):107u201314.
- Tolkacheva EG, Schaeffer DG, Gauthier DJ, Krassowska W. Condition for alternans and stability of the 1:1 response pattern in a "memory" model of paced cardiac dynamics. Physical review E, Statistical, nonlinear, and soft matter physics. 2003 Mar;67(3 Pt 1):031904.
- Neu JC, Krassowska W. Modeling postshock evolution of large electropores. Physical Review E - Statistical, Nonlinear, and Soft Matter Physics. 2003 Feb 1;67(2 1):219151u20132191512.
- Krassowska W. Field stimulation of cardiac fibers with random spatial structure. IEEE transactions on bio-medical engineering. 2003 Jan;50(1):33u201340.
- Neu JC, Krassowska W. Modeling postshock evolution of large electropores. Phys Rev E, Stat Nonlinear Soft Matter Phys (USA). 2003;67(2).
- Krassowska W, Nanda GS, Austin MB, Dev SB, Rabussay DP. Viability of cancer cells exposed to pulsed electric fields: the role of pulse charge. Annals of biomedical engineering. 2003 Jan;31(1):80u201390.
- Skouibine K, Wall J, Krassowska W, Trayanova N. Modelling induction of a rotor in cardiac muscle by perpendicular electric shocks. Medical & biological engineering & computing. 2002 Jan;40(1):47u201355.
- Skouibine K, Krassowska W. Increasing the computational efficiency of a bidomain model of defibrillation using a time-dependent activating function. Annals of biomedical engineering. 2000 Jul;28(7):772u201380.
- Oliver RA, Hall GM, Bahar S, Krassowska W, Wolf PD, Dixon-Tulloch EG, et al. Existence of bistability and correlation with arrhythmogenesis in paced sheep atria. Journal of cardiovascular electrophysiology. 2000 Jul;11(7):797u2013805.
- Bilska AO, DeBruin KA, Krassowska W. Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation. Bioelectrochemistry (Amsterdam, Netherlands). 2000 Jun;51(2):133u201343.
- Wall J, Trayanova NA, Skouibine K, Krassowska W. Modeling induction of reentry with a realistic S2 stimulus. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1999 Dec 1;1:154.
- Skouibine K, Krassowska W. Reduced bidomain model of defibrillation. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1999 Dec 1;1:287.
- Bilska AO, DeBruin KA, Krassowska W. Electroporation of single cells by high frequency shocks. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1999 Dec 1;1:87.
- Oliver RA, Krassowska W, Hall GM, Bahar S, Wolf PD, Gauthier DJ. Existence of bistability and correlation with arrhythmogenesis in sheep atria. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1999 Dec 1;1:157.
- Bahar S, Hall GM, Oliver RA, Krassowska W, Gauthier DJ. Transitions between 2:1 and 1:1 responses in cardiac muscle induced by added stimuli. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1999 Dec 1;1:258.
- DeBruin KA, Krassowska W. Modeling electroporation in a single cell. I. Effects Of field strength and rest potential. Biophysical journal. 1999 Sep;77(3):1213u201324.
- Aguel F, Debruin KA, Krassowska W, Trayanova NA. Effects of electroporation on the transmembrane potential distribution in a two-dimensional bidomain model of cardiac tissue. Journal of cardiovascular electrophysiology. 1999 May;10(5):701u201314.
- Stone BA, Lieberman M, Krassowska W. Field stimulation of isolated chick heart cells: comparison of experimental and theoretical activation thresholds. Journal of cardiovascular electrophysiology. 1999 Jan;10(1):92u2013107.
- DeBruin KA, Krassowska W. Modeling electroporation in a single cell. II. Effects of ionic concentrations. Biophys J (USA). 1999;77(3):1225u201333.
- Neu JC, Krassowska W. Asymptotic model of electroporation. Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics. 1999 Jan 1;59(3):3471u201382.
- DeBruin KA, Krassowska W. Electroporation and shock-induced transmembrane potential in a cardiac fiber during defibrillation strength shocks. Annals of biomedical engineering. 1998 Jul;26(4):584u201396.
- Roth BJ, Krassowska W. The induction of reentry in cardiac tissue. The missing link: How electric fields alter transmembrane potential. Chaos. 1998 Jan 1;8(1):204u201320.
- Krassowska W, Kumar MS. Role of spatial interactions in creating the dispersion of transmembrane potential by premature electric shocks. Annals of Biomedical Engineering. 1997;25(6):949u201363.
- Neu JC, Preissig RS, Krassowska W. Initiation of propagation in a one-dimensional excitable medium. Physica D: Nonlinear Phenomena. 1997 Jan 1;102(3u20134):285u201399.
- DeBruin KA, Krassowska W. Electroporation as a mechanism of the saturation of transmembrane potential induced by large electric fields. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1996 Dec 1;5:1836u20137.
- Krassowska W. Macroscopic model of electroporating membrane. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1995 Dec 1;17(1):253u20134.
- Trayanova N, Krassowska W. Virtual electrode effects in a bidomain model with electroporating membrane. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1995 Dec 1;17(1):255u20136.
- Walcott GP, Walker RG, Cates AW, Krassowska W, Smith WM, Ideker RE. Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation. Journal of cardiovascular electrophysiology. 1995 Sep;6(9):737u201350.
- Krassowska W. Effects of electroporation on transmembrane potential induced by defibrillation shocks. Pacing and clinical electrophysiologyu202f: PACE. 1995 Sep;18(9 Pt 1):1644u201360.
- Krassowska W. Effects of electroporation on transmembrane potential induced by defibrillation shocks. PACE - Pacing and Clinical Electrophysiology. 1995;18(9 I):1644u201360.
- Krassowska W, Neu JC. Response of a single cell to an external electric field. Biophysical journal. 1994 Jun;66(6):1768u201376.
- Alferness C, Bayly PV, Krassowska W, Daubert JP, Smith WM, Ideker RE. Strength-interval curves in canine myocardium at very short cycle lengths. Pacing Clin Electrophysiol. 1994 May;17(5 Pt 1):876u201381.
- Krassowska W, Neu JC. Effective boundary conditions for syncytial tissues. IEEE transactions on bio-medical engineering. 1994 Feb;41(2):143u201350.
- Krassowska W, Neu JC. Boundary conditions for the bidomain model of the heart. Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1993 Dec 1;15(pt 2):865u20136.
- Guse PA, Rollins DL, Krassowska W, Wolf PD, Smith WM, Ideker RE. Effective defibrillation in pigs using interleaved and common phase sequential biphasic shocks. Pacing and clinical electrophysiologyu202f: PACE. 1993 Aug;16(8):1719u201334.
- Neu JC, Krassowska W. Homogenization of syncytial tissues. Critical reviews in biomedical engineering. 1993 Jan;21(2):137u201399.
- Krassowska W, Cabo C, Knisley SB, Ideker RE. Propagation versus delayed activation during field stimulation of cardiac muscle. Pacing and clinical electrophysiologyu202f: PACE. 1992 Feb;15(2):197u2013210.
- Krassowska W, Rollins DL, Wolf PD, Dixon EG, Pilkington TC, Ideker RE. Pacing thresholds for cathodal and anodal high-frequency monophasic pulses. Journal of Cardiovascular Electrophysiology. 1992 Jan 1;3(1):64u201376.
- Krassowska W, Pilkington TC, Ideker RE. Two-scale asymptotic analysis for modeling activation of periodic cardiac strand. Mathematical and Computer Modelling. 1992 Jan 1;16(3):121u201330.
- Knisley SB, Krassowska W, Pilkington TC, Smith WM. Do myocardial fibers contain junctional capacitance? Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1991 Dec 1;13(pt 2):611u20132.
- Papanicolaou VG, Krassowska W. Electrostatic potential on the boundary of cardiac tissue. Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1991 Dec 1;13(pt 2):500u20131.
- Ideker RE, Wolf PD, Alferness C, Krassowska W, Smith WM. Current concepts for selecting the location, size and shape of defibrillation electrodes. Pacing and clinical electrophysiologyu202f: PACE. 1991 Feb;14(2 Pt 1):227u201340.
- Krassowska W, Morrow MN, Pilkington TC. Modeling in the Bioelectric Stimulation Unit. Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1990 Dec 1;(pt 2):666u20137.
- Krassowska W, Knisley SB, Pilkington TC, Ideker RE. Modeling high-frequency pacing with a discrete cardiac strand. Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1990 Dec 1;(pt 2):624u20135.
- Knisley SB, Krassowska W, Pilkington TC, Smith WM. Effect of intercellular capacitance on conduction in a model of cell uncoupling. Proceedings of the Annual Conference on Engineering in Medicine and Biology. 1990 Dec 1;(pt 2):620u20131.
- Krassowska W, Pilkington TC, Ideker RE. Potential distribution in three-dimensional periodic myocardium--Part I: Solution with two-scale asymptotic analysis. IEEE transactions on bio-medical engineering. 1990 Mar;37(3):252u201366.
- Krassowska W, Frazier DW, Pilkington TC, Ideker RE. Potential distribution in three-dimensional periodic myocardium--Part II: Application to extracellular stimulation. IEEE transactions on bio-medical engineering. 1990 Mar;37(3):267u201384.
- Ideker RE, Frazier DW, Krassowska W, Shibata N, Chen PS, Kavanagh KM, et al. Experimental evidence for autowaves in the heart. Annals of the New York Academy of Sciences. 1990 Jan;591:208u201318.
- Ideker RE, Krassowska W, Wharton JM, Smith WM. Experimental results pertinent to the modelling of defibrillation. Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings. 1989 Nov 1;11 pt 1:77u20138.
- Krassowska W, Pilkington TC, Ideker RE. Modelling the periodicity of cardiac muscle. Journal of electrocardiology. 1989 Jan;22 Suppl:41u20137.
- Frazier DW, Krassowska W, Chen PS, Wolf PD, Danieley ND, Smith WM, et al. Transmural activations and stimulus potentials in three-dimensional anisotropic canine myocardium. Circulation research. 1988 Jul;63(1):135u201346.
- Frazier DW, Krassowska W, Chen PS, Wolf PD, Dixon EG, Smith WM, et al. Extracellular field required for excitation in three-dimensional anisotropic canine myocardium. Circulation research. 1988 Jul;63(1):147u201364.
- Krassowska W, Tang ASL, Pilkington TC, Ideker RE. Anodal and cathodal thresholds during transthoracic stimulation. IEEE/Engineering in Medicine and Biology Society Annual Conference. 1988 Jan 1;10(pt 1):202u20133.
- Krassowska W, Frazier DW, Pilkington TC, Ideker RE. Finite element approximation of potential gradient in cardiac muscle undergoing stimulation. Mathematical and Computer Modelling. 1988 Jan 1;11(C):801u20136.
- Pilkington TC, Krassowska W, Morrow MN, Ideker RE. FEASIBILITY OF ESTIMATING ENDOCARDIAL POTENTIALS FROM CAVITY POTENTIALS. IEEE/Engineering in Medicine and Biology Society Annual Conference. 1987 Dec 1;1875u20136.
- Krassowska W, Pilkington TC, Ideker RE. The closed form solution to the periodic core-conductor model using asymptotic analysis. IEEE transactions on bio-medical engineering. 1987 Jul;34(7):519u201331.
- Krassowska W, Pilkington TC, Ideker RE. Periodic conductivity as a mechanism for cardiac stimulation and defibrillation. IEEE transactions on bio-medical engineering. 1987 Jul;34(7):555u201360.
- Krassowska W, Pilkington TC, Ideker RE. ASYMPTOTIC ANALYSIS FOR PERIODIC CARDIAC MUSCLE. IEEE/Engineering in Medicine and Biology Society Annual Conference. 1986 Dec 1;255u20138.
- Krassowska W, Jurkiewicz B, Klupsz E, Peczalski K, Stopczyk M. Computerized system for isochronic epicardial mapping. Medical Informatics. 1985;10(3):237u201345.
- Neu WK. Analytical solution for time-dependent potentials in a fiber stimulated by an external electrode (Submitted). Medical & Biological Engineering & Computing.
- Neu WK. Uncertainty in 1D and 3D models of a fiber stimulated byan external electrode (Submitted). In.
- Neu WK, Neu JC. Modeling electroporation with moment dynamics equations (Accepted). In.
- Neu WK. Analytical solution for time-dependent potentials in a cylindrical fiber. In.