Cells and tissues in our body change how they metabolize nutrients like sugars, amino acids, and fats during disease such as cancer, diabetes, or metabolic syndromes. These nutrients, also called metabolites, must be taken up from circulation and require specific transporters to do so. One of the main areas of research within my group involves identifying and characterizing specific transport proteins that are required by cells to fulfill their metabolic needs. Within this objective, we aim to understand what drives selective transporter expression in disease, how transporters function in specific physiological contexts, and how we can target the unique metabolic demands of cancer. We utilize biochemical and molecular biology techniques and develop quantitative mass spectrometry-based methods that include targeted and discovery metabolomics, stable-isotope tracing, and metabolic flux analysis to characterize the fate of key nutrients in diseased cells.
Better tools to study amino acid metabolism and transport in intact cells. There are ~450 solute carrier (SLC) transporters that participate in the import and efflux of ions, amino acids, sugars, and cofactors required for metabolism. However, over 30% of these SLCs are uncharacterized or poorly understood. Our research group is currently developing better molecular biology, imaging, and metabolomics tools that aim to advance our understanding of the function, localization, and cooperativity of amino acid transporters through uncoupling of transport from intracellular metabolism.
Understand the metabolic advantage of selective, compartment-specific enzyme expression. The metabolic pathways that comprise eukaryotic metabolism are compartmentalized into distinct and specialized organelles (e.g. mitochondria, lysosomes, peroxisomes). Current metabolomics methods that extract bulk cellular metabolites fail to capture the compartmentalization of intracellular metabolism. Our group aims to develop better methods to interrogate compartmentalized metabolic pathways. In this vein, we hope to understand how expression of specific enzyme isoforms may offer a selective advantage for cancer cells.
Metabolic and transporter dependencies in childhood leukemia. Therapies that target the unique metabolism of leukemic blasts have demonstrated remarkable clinical success. However, toxicities can often limit the efficacy of anti-metabolic therapies and relapse of therapeutic-resistant cancer can occur. My group aims to identify metabolic dependencies in childhood leukemia with a specific focus on relapsed cases. Furthermore, we are interested in targeting metabolite transport as a more direct approach over systemic metabolite depletion therapies that are currently employed.