In more than 35 years of research Walsh has studied a variety of enzymes, a class of proteins in humans and other organisms that orchestrate the breakdown of food, the assembly of hormones, the coagulation of blood, and the processing of neurological signals and many other functions.
"We're interested in what enzymes actually do, how they do it, what goes wrong and whether we can fix it," said Walsh, a biological chemist and professor at Harvard Medical School. About one-third of human diseases start with some malfunction in one of the body's thousands of enzymes.
Most recently his research team has focused on antibiotics, drugs that fight bacterial infections by selectively blocking bacterial enzymes while leaving human ones alone. For example, vancomycin kills bacteria by inhibiting their enzymes' ability to stitch together their cell walls.
In the early 1990s Walsh and his group discovered and characterized how some bacteria were able to evolve resistance to vancomycin's action -- by changing the shape of their strands of cell wall. Their fundamental insights have helped drug companies design new variants of vancomycin, some of which are now in human trials.
Walsh, who originally planned to go to medical school after college, was an undergraduate researcher in the laboratory of Konrad Bloch when he won the Nobel Prize in Physiology or Medicine in 1964 for his cholesterol research. "I'm sure that had something to do with my deciding I liked research better," Walsh said.