Metabolic programming in tissue development, homeostasis and disease
The maintenance of metabolic homeostasis depends on proper programming of nutrient and energy metabolism in tissues. Adult tissues are highly specialized in their metabolic functions, yet at the same time exhibit a remarkable degree of plasticity. By dissecting the molecular and genetic underpinnings of metabolic programming, we gain insights into how energy metabolism is specified during tissue development, how nutrient signaling impinges on key metabolic pathways, and how altered nutrient and energy metabolism leads to obesity, type 2 diabetes, and fatty liver disease.
We have discovered epigenetic mechanisms mediated by chromatin-remodeling complexes that drive the formation and function of oxidative and glycolytic muscle. We have expanded the regulatory code beyond protein factors and revealed long non-coding RNAs (lncRNAs) in the control of brown and beige adipocyte differentiation and metabolism. We have gained insights into the mechanisms that govern circadian control of metabolic rhythms.
Metabolic crosstalk via secreted factors
Cells and tissues do not exist in isolation in the body; instead, they are constantly exposed to the ebb and flow of nutrients and hormones and release factors that serve as metabolic signals. By discovering new secreted hormones, we illustrate the concept that a distributed endocrine signaling network serves important functions in the regulation of metabolic physiology and homeostasis. We combine global profiling and single-cell analysis to identify novel ligands and receptors, investigate their role in metabolic crosstalk and explore the potential of developing biologic therapeutics for the treatment of metabolic disease.