For the past 40 years, John Wikswo has worked on measurements and modeling in bioengineering and electrophysiology, initially at the scale of humans and dogs, then with rodents, and more recently at the level of nanoliter bioreactors and individual cells. He explored in depth the relationship between cardiac electric and magnetic fields and the generation of the vector magnetocardiogram. With his collaborators, he made the first measurements of the magnetic field of a single axon and a single skeletal muscle fiber. All of these studies provided key insights into the parameters that relate the intracellular action currents to the transmembrane potential and extracellular electric and magnetic fields. His group played a central role in demonstrating the part performed by tissue anisotropy in the response of cardiac tissue to strong electric shocks and the behavior of cardiac virtual electrodes, which are explained by the doubly anisotropic bidomain of cardiac electrical activity. He also participated in pioneering magnetic measurements of the magnetoenterogram, a non-invasive recording of the magnetic field of the electrical activity in the human gastrointestinal tract. He then spent a decade exploring the capabilities of superconducting quantum interference device (SQUID) magnetometers for non-destructive testing of plastics and corroding aluminum.

He is the founding Director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), which was created in 2001 with a $5 million, five-year grant from the Vanderbilt Academic Venture Capital Fund to foster and enhance interdisciplinary research in the biophysical sciences, bioengineering, and medicine at Vanderbilt. Within VIIBRE, he has focused on building on-campus collaborations to use microfabrication to create and utilize devices to instrument and control single cells and small collections of cells, and to provide data for parameterization of models of biological processes. In the past 13 years, VIIBRE has played a central role in bringing to Vanderbilt grants and contracts totaling more than $70 million.