After earning his Ph.D. in Pharmacology from Loyola University in 1979, John Williams worked as a research scientist at the Max-Planck Institute in Munich and at Loyola University School of Medicine. He then spent five years as a research scientist in Biological Sciences at the Massachusetts Institute of Technology. In 1987, he became an assistant scientist at the Vollum Institute and rose to the position of senior scientist in 1996. He holds a concurrent appointment in the Department of Physiology and Pharmacology in the School of Medicine.

Williams and colleagues investigate the early events that lead to the development of tolerance to opioids. Opioids such as morphine are important therapeutic compounds used for the management of pain, but the primary problem with their use is the development of tolerance, where higher doses are required to achieve the same effect. By focusing on the long-term effects of morphine and cocaine on synaptic transmission in the reward centers of the brain—dopamine cells of the ventral tegmental area and GABA cells of the nucleus accumbens—the lab hopes to identify the cellular basis for drug addiction.