Building Community to Advance Metabolic Science

Mitochondria and intermediary metabolism are central to health and disease, yet many of us learn a simplified version of this complex science. To develop expertise in metabolism research at Yale School of Medicine (YSM), Richard Kibbey, MD, PhD, professor of medicine (endocrinology and metabolism), created the Program for Mitochondrial Biology and Intermediary Metabolism (MBIM).

Mitochondria are key to the regulation of tissue function, such as insulin secretion, glucose production, nerve transmission, muscular contraction, and inflammation as well as cancer cell growth, Kibbey explains. The term “intermediary” refers to the compounds—the chemical metabolites—that are going through and transformed by the metabolic pathways.

There are a lot of misconceptions about how to measure mitochondrial function and metabolism and the meaning of various observations, Kibbey notes. “The educational component of MBIM will promote a deeper understanding of the fundamental mechanisms of mitochondrial metabolism and chemical biology, and how to design, perform, and interpret studies,” he said.

The goal of the program, which Kibbey launched in early 2023, is to catalyze collaboration, provide education, promote publications, offer innovative technologies, and help investigators obtain funding.

“Many labs across YSM are interested in studying metabolism, but they’re somewhat disconnected from each other,” Kibbey said. “I want to bring that community together and develop stronger resources to further metabolism studies that will challenge many assumptions we’ve made over the past 30 to 40 years and expand our understanding of metabolism.”

Cutting-edge technologies currently offered through the Chemical Metabolism Core component of MBIM measure targeted and untargeted metabolomics, cellular respiration, and metabolic fluxes using stable isotope labeled samples. Due to demand among investigators, Kibbey is working to add a new lipidomics facility that will measure many lipid species and their side chains quantitatively. These core services are offered to researchers at cost.

MBIM is already supporting a multi-institution grant that supports a large study involving stable isotope labeling and metabolomics to explore the intersection among diet, sex, genetics, and metabolism across multiple tissues, according to Kibbey. “That is one example of the types of projects that we hope to continue to develop,” he said.

The need to understand mitochondrial biology is of critical importance to our understanding of metabolic homeostasis and disease, said Anton Bennett, PhD, Dorys McConnell Duberg Professor of Pharmacology and professor of comparative medicine.

“This new program will provide the platform from which investigators can tackle questions relating to how mitochondrial function and regulation impacts metabolism,” Bennett said. “The expertise and instrumentation that the program provides in the area of mitochondrial biology fulfils an unmet research need and is anticipated to be of high impact across the medical school.”

“This program will be very important to our growing portfolio of metabolism research,” said Nancy J. Brown, MD, Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal Medicine.

As MBIM continues to build the metabolism community and draw connections across disciplines, Kibbey envisions the program supporting opportunities for retreats, seminar series, instrument educational workshops, collaborative papers, and grants.

“We’re very eager to help people design, carry out, and interpret their metabolism studies to advance outstanding interdisciplinary metabolic science at Yale,” he said.

Yale School of Medicine’s Section of Endocrinology and Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more, visit Endocrinology and Metabolism.