Organic Chemistry Seminar
Charlie Fehl received a B.S. in Biochemistry from the University of Michigan in 2009 and a Ph.D. in Medicinal Chemistry from the University of Kansas in 2014. After conducting postdoctoral research at the University of Oxford on protein modification methodology development, he opened his independent research lab at Wayne State University in 2018. The Fehl Lab builds chemically-controlled tools for glycobiology studies. We also have a dedicated disease project platform that investigates how hyperglycemia can lead to diabetes and different tumor types using a combination of in vitro and in vivo models, offering a diverse set of skills to train a next generation of chemical biology innovators.
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.
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