Capturing Hearts and Minds: Data–Driven Approaches to Modelling Cardiac and Neural Electrophysiology
Senior Research Scientist
University of Oslo
April 2, 2018
Foege N130A, Wallace H. Coulter Seminar Room
Andy’s work integrates experimental and computational approaches to understand the processes controlling electrical function and dysfunction in the heart and brain. In this talk he will describe four projects that apply these approaches at various levels of physiology. The first 2 projects employ classical whole cell- and single ion channel- recordings to build ODE-based computational models of individual ion channels and whole cardiac myocytes. These models were used to identify a new role for sodium channel reactivation in repolarization instability, and to investigate the potential for pharmacologic blockade of small conductance calcium-activated potassium channels in atrial fibrillation. The third and fourth projects are broader in scope, and utilize more recent advances in microscopy as a foundation for model generation and interrogation. Project 3 employs super-resolution light microscopy to build 3-dimensional models of the ultrastructures involved in cardiac excitation-contraction coupling. These structures are degraded in chronic cardiac disease, and we use simulations to distinguish the outcomes of this degradation from the many simultaneous changes present in experimental disease models. Finally, the fourth project makes use of human induced pluripotent stem cells (h-iPSCs). Here cell-level electrophysiologic models serve as a bridge to span the functional differences between the differentiation products of these cells (h-iPSC-derived myocytes and neurons), and the cardiac myocytes and neurons present in vivo.
After brief early research experiences with human studies in exercise biology and biomechanics, Andy took his PhD in Integrative Physiology exploring the cellular mechanisms of cardiac infarct resistance with Professor Russ Moore at the University of Colorado at Boulder. That work developed a particular focus on electrophysiologic mechanisms, and the role of ATP-sensitive potassium channels in protecting the heart from ischemic damage. Over the course of those rodent studies he was struck by the uncertainties introduced by the separation of measurements across temporal and spatial scales, and resolved to pursue his postdoctoral training in multiscale modeling with Professor Andrew McCulloch at UCSD. There he developed a strong interest in designing interactive studies involving both experimental and computational arms, and this has remained the major characteristic of his scientific approach. Today Andy’s research covers a range of topics in cardiac and neural electrophysiology, and has expanded further into the computational domain through coordinating an international doctoral program in computational biology and medicine.