Organic Chemistry Seminar

All cells use glucose. However, unregulated glucose levels in metabolic disease, diet, or genetic disposition can lead to increased disease risk for type 2 diabetes, cardiovascular diseases, and several types of cancer. Despite the importance of these pathologies, it is challenging to identify molecular targets that link hyperglycemia to disease risk. Our lab develops chemical tools to study the effects of high sugar on cellular pathways, including in animal and tissue models. We developed light-controlled sugar substrates, biochemical labeling systems for sugars, and chemical probes to control and track sugar patterns in cells.

Specifically, we examine protein glycosylation, focusing on O-linked N-acetylglucosamine (O-GlcNAc) and N-linked sialic acid sugars, such as NeuAc. We find that hyperglycemia can enhance breast cancer risk through activating cancer stem cell pathways and the protein TET1. In another study, we find that migration of ovarian cancer tumors from the ovaries to the adipose tissue upregulates sugar levels on cell surfaces, increasing tumor immune evasion and aggression. To treat these disease states, one current focus is on designing inhibitors for sugar-transfer enzyme targets that we discovered in cancer stem-like cells. Another focus is repurposing a nutrient transporter drug to disrupt the fatty acid-based reprogramming pathway we discovered in ovarian cancer adipose metastasis. We aim to specifically disrupt the pathological links we find between metabolic disease, hyperglycemia, and cancer risk without affecting normal metabolic homeostasis.