Metabolism is a fundamental biological phenomenon. Dysregulated metabolism contributes to a variety of disease, including cancer and diabetes, which are known as metabolic disease. Metabolic alteration has been studied at several levels, from the whole organism to the single cells and subcellular organelles. The balance between energy intake and energy expenditure controls the body weight gain; while all the organs in our body have their own metabolic feature. Each organ contains several kinds of cell types with different metabolism, and tumor is also famous for its metabolic heterogeneity. Even within the cells, all kinds of nutrient are used to provide the support for basic cellular activities, including survival, mobility and growth.
A major goal of my research is to explore the coordinated metabolic adaptation under both normal physiological and specific pathological conditions. Metabolic reactions have their spatial and temporal distribution, which is also known as cellular compartmentation. A wide variety of cell types present in both the adipose tissue of diabetic patients and the tumor of cancer patients, and their metabolism actively communicates with each other, which is another layer of compartmentation. Metabolites, like citrate and serine, are well known for their nutrient role, and they can also serve as signal molecule between the cells and within the subcellular structure. My recent study showed that a novel cytosol-to-mitochondria citrate transport system mitigates the mitochondrial oxidative stress in the detached cancer cell, and we will look into the signaling control between the subcellular organelles.
With the aim of precision medicine, biology becomes a data-rich science. While the genetic heterogeneity is widely accepted with the easy access to the large sequencing data, the metabolic heterogeneity has also been more appreciated with the evolution of the analytical tools. The integration of mass spec based metabolic tracing and mathematical bioengineering based modeling prediction will provide a new angle to understand the metabolic rewiring in diabetes, cancer and other diseases. A better knowledge of the central carbon metabolism, amino acid utilization and nucleic acid synthesis will lead to new diagnostic approach and potential novel drug target.