Address

5101 Cass Ave., Detroit, MI 48202

Office Address

  Office: 469 Chem

Department

 Chemistry

Laboratory Address

Lab: 460 Chem

Laboratory Web Site

https://fehl-lab.com/

Research Interests

• Chemical tools to track how glycans change spatiotemporally during cell metabolism and signaling
• Biochemical studies to discover and predict functional effects of protein glycosylation
• Medicinal chemistry to inhibit metabolic risk factors in tumorigenic pathways

Research Description

All cells use sugar, but a consequence of unbalanced sugar usage is disease through hexosamine sugar signaling pathways including glucosamines. To precisely define the roles of hexosamine sugar-driven effects, the Fehl Group designs chemical tools sensitive for live-cell applications, for example our light-controlled photosugars and our cell compartment-specific "GlycoID" labeling strategy. We apply chemical biology tools at the interface of metabolism disease and cancer pathways to discover new roles for glucose-driven events in cells and disease. A key target area is determining the mechanisms and potential treatment strategies for cancers that have elevated risk in patients with hyperglycemia.

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.

Recent Publications

“Adipose microenvironmental reprogramming of ovarian cancer cells to an immune-hardened high sialic acid glycosylation state.” Alexandra Fox†, Garry D. Leonard† († co-first), Nicholas Adzibolosu, Sapna Sharma, Terrence Wong, Roslyn Tedja, Radhika Gogoi, Robert Morris, Gil Mor, Charlie Fehl*, Ayesha B. Alvero*. (*correspondence) Frontiers in Oncology, submitted. Online on bioRxiv at: https://doi.org/10.1101/2024.05.13.593990

“GlycoID Proximity Labeling to Identify O-GlcNAcylated Protein Interactomes in Live Cells.” Zachary M. Nelson, Oseni Kadiri, and Charlie Fehl. Current Protocols in Chemical Biology (2024), 4, doi: https://doi.org:10.1002/cpz1.1052

“Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways.” Nelson, Zachary M.; Leonard, Garry D.; Fehl, Charlie. Journal of Biological Chemistry (2024) 300: pg. 105615. doi: https://doi.org/10.1016/j.jbc.2023.105615

Saheed Ayodeji, Emily A. Teslow, Lisa A. Polin, Greg Dyson, Aliccia Bollig-Fischer, and Charlie Fehl. Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. Cancer Cell International 2023;23:102.

Yimin Liu, Zachary M. Nelson, Ali Reda, and Charlie Fehl. Spatiotemporal Proximity Labeling Tools to Track GlcNAc Sugar-Modified Functional Protein Hubs during Cellular Signaling. ACS Chemical Biology 2022;17:2153.

Courtney A. Kon dor, Jaggaiah N. Gorantla, Garry D. Leonard, and Charlie Fehl. Synthesis and mammalian cell compatibility of light-released glycan precursors for controlled metabolic engineering. Bioorganic & Medicinal Chemical 2022;70:116918.

Charlie Fehl and John A. Hanover. Tools, Tactics, and Objectives to Interrogate Cellular Roles of O-GlcNAc in Disease. Nature Chemical Biology 2022;18:8-17.

Groenevelt, Jessica M.; Corey, Daniel J.; Fehl, Charlie. Chemical Synthesis and Biological Applications of O-GlcNAcylated Peptides and Proteins. ChemBioChem 2021;22:1854-70.

Josephson, Brian*; Fehl, Charlie*; Iseneggar, Patrick* [*equal contributors]; Nadal, Simon; Wright, Tom H.; Poh, Adeline W.J.; Bower, Ben J.; Giltrap, Andrew M.; Chen, Lifu; Batchelor-McAuley, Christopher; Roper, Grace; Arisa, Oluwatobi; Sap, Jeroen B.I.; Kawamura, Akane; Baldwin, Andrew; Mohammed, Shabaz; Compton, Richard G.; Gouverneur, Veronique; Davis, Benjamin. G. Mild, Light-Driven, Posttranslational Installation of Reactive Protein Side-Chains. Nature 2020;585: 530.

Yang, Min*; Fehl, Charlie* [*equal contributors]; Lees, Karen V.; Lim, Eng-Kiat; Offen, Wendy; Davies, Gideon J.; Bowles, Dianna J.; Roberts, Stephen J.; Davis, Benjamin G. Functional and informatics analysis enables glycosyltransferase activity prediction. Nature Chemical Biology 2018;14:1109.

Fehl, Charlie; Vogt, Caleb; Yadav, Rahul; Li, Kelin; Scott, Emily E.; Aubé, Jeffrey. Structure-based design of inhibitors with improved selectivity for steroidogenic cytochrome P450 17A1 over cytochrome P450 21A2. J. Med. Chem. 2018;61:4946.

Education/Training

Postdoc, 2018, University of Oxford - Chemical Biology
Ph.D. 2014, University of Kansas - Medicinal Chemistry
B.S. 2009, University of Michigan - Biochemistry

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