Discovering new strategies for targeting elevated glucose consumption in cancer
Elevated glucose consumption, or the Warburg Effect, is fundamental to nearly all cancer. The Warburg Effect was one of the first molecular phenotypes discovered about cancer and forms the basis of 18F-FDG PET imaging, which is used routinely the visualize cancer in the clinic. Despite being known for almost 100 years, the Warburg Effect has proven incredibly challenging to drug. We recently developed a high-throughput assay for measuring cellular glucose consumption that is over 100-fold faster than traditional assays. With this assay, we can now evaluate thousands of small molecules or proteins at a time to discover what mechanisms cancer cells use to drive glucose consumption, how these mechanism compare to what happens in healthy tissues, and which proteins or pathways should be targeted to selectively block cancer cell glucose consumption. Our goal is to leverage this information to develop selective inhibitors of cancer cell glucose consumption.
Studying immunometabolism in vivo with positron emission tomography (PET) to identify new targetable pathways for modulating the immune system
Metabolism is fundamental to immune cell function. Changes in the level of intracellular or extracellular metabolites can have a profound effect on the development and function of the immune system. Additionally, the immune system is a complex, dynamic organ with heterogeneity in its composition and function over space and time. Despite this, many studies on immunometabolism are carried out in isolation in cell culture. We strive to understand immunometabolism in living organisms. To do this, we use an advanced molecular imaging technology called positron emission tomography (PET). With PET, we are able to study the metabolism of different immune cell types at distinct anatomical locations throughout the organism. We apply this technology to the study of autoimmune disorders with the goal of developing new metabolism-based therapies to treat these challenging diseases.