Wayne State University

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College of Liberal Arts & Sciences
Department of Chemistry
Faculty Page
 
Charlie Fehl
Title Assistant Professor
Division Biochemistry
Education B.S., University of Michigan, 2009
Ph.D., University of Kansas, 2014
Postdoctoral Research Associate, University of Oxford, UK, 2014-2018
Office Chem 469
Phone (313)577-5667
E-Mail
Group https://fehl-lab.com


The Fehl Lab develops chemical tools to target ongoing biological processes in living systems. This "bioorthogonality" enables real-time insight into signaling pathways that actively alter gene expression profiles (epigenetic effects) in cells as their environment changes. We use these insights to develop pharmacological probes, which are tested in disease model systems for therapeutic effects.
 

Our key target is the protein O-GlcNAc modification (serine/threonine O-linked N-acetylglucosamine), which modifies proteins as a glucose sensor. Thousands of proteins are known to be O-GlcNAcylated, including many transcription factors that regulate gene expression. In humans, only one enzyme adds O-GlcNAc (O-GlcNAc transferase, OGT) and only one enzyme removes O-GlcNAc (O-GlcNAc hydrolase, OGA). Thus, downstream pathways/mechanisms are needed to successfully separate therapeutically useful targets from healthy processes.
 


 

  1. Chemical biology tools to identify protein O-GlcNAcylation in living cells. We develop tools to avoid disrupting cellular metabolism/physiology that rely on bioorthogonal activation for sensitive protein labeling.
     

     
  2. Machine-learning strategies to identify distinct and separable disease targets. We use deep informatic approaches to implicate specific target pathways involved in context-dependent O-GlcNAc signaling.
     

     
  3. Design and synthesis of glycopeptidomimics as inhibitors of O-GlcNAcylated protein binding partners for therapeutic action. Modification allow chemoproteomic profiling of specific interaction partners.
     

     

Dr. Charlie Fehl is a synthetic chemical biologist. His training--spanning the Atlantic ocean at times (University of Michigan / University of Kansas / Universität Regensburg (Germany) / Oxford University (United Kingdom))--focused on chemical techniques in catalyst design, photochemistry, and biocatalysis. These were applied to solve problems in drug design, protein synthesis + modification, epigenetic protein-protein interactions, and understanding complex enzymatic networks. Researchers in the Fehl Lab will develop selective chemical and biochemical tools to unravel and treat complex problems in disease biology.
 

 


JOURNAL ARTICLES

  1. "Functional screening and chemo-bioinformatic analysis allows rationalization and activity prediction within a broad protein family." 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. Nature Chemical Biology, Accepted (2018).
  2. "Structure-based design of inhibitors with improved selectivity for steroidogenic cytochrome P450 17A1 over cytochrome P450 21A2." Fehl, Charlie; Vogt, Caleb; Yadav, Rahul; Li, Kelin; Scott, Emily E.; Aubé, Jeffrey. J. Med. Chem. 2018, 61, 4946. DOI: 10.1021/acs.jmedchem.8b00419
  3. "Proteins as templates for complex synthetic metalloclusters: towards biologically programmed heterogeneous catalysis." Fehl, Charlie; Davis, Benjamin G. Proc. Royal Soc. A: Math. Phys. Eng. Sci. 2016, 472, 20160078. DOI: 10.1098/rspa.2016.0078
  4. "Temperature dependence of turnover in a Sc(OTf)3-catalyzed intramolecular Schmidt reaction." Fehl, Charlie; Hirt, Erin. E.; Li, Sze-Wan; Aubé, Jeffrey. Tetrahedron Lett. 2015, 56, 3137. DOI: 10.1016/j.tetlet.2014.12.068
  5. "Photocatalytic surface patterning of cellulose using diazonium salts and visible light." Schroll, Peter; Fehl, Charlie; Dankesreiter, Stefan; König, Burkhard. Org. Biomol. Chem. 2013, 11, 6510. DOI: 10.1039/c3ob40990b
  6. "Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction." Motiwala, Hashim F.; Fehl, Charlie; Li, Sze-Wan; Hirt, Erin E.; Porubsky, Patrick; Aubé, Jeffrey. J. Am. Chem. Soc. 2013, 135, 9000. DOI: 10.1021/ja402848c
  7. "Use of a tandem Prins/Friedel-Crafts reaction in the construction of the indeno-tetrahydropyridine core of the haouamine alkaloids: formal synthesis of (-)-haouamine A." Fenster, Erik; Fehl, Charlie; Aubé, Jeffrey. Org. Lett. 2011, 13, 2614. DOI: 10.1021/ol200725m

 

 
BOOK CHAPTERS

  1. "Outperforming Nature's Catalysts: Designing Metalloenzymes for Chemical Synthesis." Fehl, Charlie; Jarvis, Amanda G.; Palm-Espling, Maria; Davis, Benjamin G.; Kamer, Paul C.J. In Modern Developments in Catalysis; World Scientific Press: Singapore, 2016; 89-122.
  2. "Hofmann, Curtius, Schmidt, Lossen and Related Reactions." Fehl, Charlie; Liu, Ruzhang; McCleod, Michael; Motiwala, Hashim; Aubé, Jeffrey. In Comprehensive Organic Synthesis, 2ndEd; Elsevier Limited: Amsterdam, 2014; 598-635.

 

 
PATENTS

  1. "Inhibitors of CYP17A1." Fehl, Charlie; Scott, Emily E.; Aubé, Jeffrey. United States Patent 9,611,270. (April 4, 2017)


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