With tracers, you can view biology like a traffic map. “You’re looking at the system from the outside, watching how the body responds to, say, a new drug. How it moves through the body to treat a disease,” Amalia Gastaldelli says. “But you can measure almost anything. Glucose production, energy expenditure, how muscle mass is built up or broken down—it’s the application of engineering techniques to study human physiology.”
This was Gastaldelli’s first love: complex systems. She grew up in a town in the Italian Alps, where her father was the head of their local emergency department and a sports medicine doctor. They spent winters cross-country skiing and summers sailing in the Adriatic, and Gastaldelli remembers first learning about physiology in quiet conversations with her father. “He was very inspiring to me,” she says. “We were always chatting and I was always curious.”
Still, Gastaldelli ultimately decided not to pursue a medical career. She earned a degree in electrical engineering from the University of Padua in Italy—one of the oldest universities in the world—and originally planned to work in signal transmission. But during her studies, she worked with Claudio Cobelli, professor in biomedical engineering, and this shone a new light on her old interest. With a renewed focus on human systems, she wrote her thesis on mathematical models for the kinetics of the amino acid leucine.
She went on to earn a PhD in biomedical engineering from the Polytechnic University of Milan, but the real change in her career was when she met Professor Robert Wolfe, a pioneer in the use of tracers to study human physiology. She attended the University of Texas Medical Branch in Galveston, TX, to earn a second PhD in human physiology and metabolism under his supervision.
“I learned that the study of complex systems requires a logical approach. A system-wide view. Nothing stands alone,” she says. “There are many causes that explain metabolic alterations, internal and external to the human body. A disturbance in one place will have an impact somewhere else.”
Gastaldelli is now a research director at the Institute of Clinical Physiology (IFC) of the National Research Council (CNR) in Pisa, Italy, where she heads the Metabolic Diseases Group and Multi-Omics Mass Spectrometry Laboratory. She is also an adjunct professor of medicine at the Diabetes Division of University of Texas Health, in San Antonio, TX, and president of both the European Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) study group and the European Group for the Study of Insulin Resistance.
Her research focuses on understanding the pathophysiological mechanisms of metabolic diseases, mainly MASLD, obesity, and type 2 diabetes, combining tracer techniques with the mathematical models she learned during her PhD work to study the alteration of metabolic fluxes as well as the secretion and action of hormones like insulin and incretins.
“You need to look at the system from different angles and with different approaches. For example, diabetic hyperglycemia could have multiple causes, including excess hepatic glucose production, reduced glucose utilization, or impaired insulin secretion and action,” she says. “Once we have a more complete map of these biological interactions, we can work on prevention and treatment.”
Recently, she became interested in how environmental factors can affect conditions like obesity and MASLD. “Endocrine disruptors, like microplastics, can also have an effect on human metabolism, especially in the liver,” she says.
“This was my dream,” she adds. “Drawing on my experiences to unravel the secrets of physiology.”
