Richard Kibbey, MD, PhD

Dr. Kibbey is a clinically-active physician scientist focused on metabolic diseases, particularly mitochondrial metabolism and metabolic signaling. His research revealed mitochondrial GTP (mtGTP) as a key part of the glucose-sensing mechanism in pancreatic beta-cells, leading to the identification of the PEP cycle—a metabolic circuit involving pyruvate kinase, pyruvate carboxylase, mitochondrial PEPCK, and the GTP isoform of succinyl CoA synthase. This pathway enables glucose concentration sensing and resolves the limitations of the traditional beta-cell glucose sensing model by aligning KATP channel closure with PEP cycling.

Furthermore, Pyruvate Kinase was identified for its role in mitochondrial ADP privation- a metabolic signal that repurposes mitochondria function from OxPhos to biosynthesis and signaling a high energy state. Targeting this process in vivo boosts glucosestimulated insulin secretion, preserves beta-cell health, reduces hepatic gluconeogenesis, and improves insulin sensitivity. The Kibbey lab is working to translate these findings into a new class of obesity therapies.

Dr. Kibbey’s graduate training at UTSW was in NMR protein structure and dynamics. At Yale, his expertise expanded to include 13C mass spectrometry, islet biology, hepatic metabolism, insulin resistance and secretion, and bioenergetics, with applications to cellular, cancer, and animal models. His lab developed the Mass Isotopomeric Multi-Ordinate Spectroscopic Analysis (MIMOSA) platform using LC/MS/MS to interpret isotopomer patterns from mitochondrial metabolism. He directs the program in Mitochondrial Biology and Intermediary Metabolism as well as the university’s Chemical Metabolism Core, which measures islet function, oxygen consumption, metabolomics, and metabolic flux using MIMOSA. Dr. Kibbey co-founded Elucidata, providing the Polly biomedical omics data platform, and State 4 Therapeutics, focused on oral small molecules for obesity treatment.

Dr. Kibbey is also committed to mentorship and education. He is Associate Director for the graduate program in Translational Biomedicine and co-director of graduate studies, having mentored or co-mentored numerous trainees, including undergraduates, medical students, residents, graduate students, and postdocs—many of whom have advanced to academic and research careers. He has served on >19 thesis committees and currently leads a group of graduate, masters, and postdoctoral trainees. He co-directs the Mitochondrial Bioenergetics and Intermediary Metabolism course, actively contributes to the Yale Center for Molecular and Systems Metabolism, and co-directs the graduate level course in Mitochondrial Biology and Intermediary Metabolism.