A collection of FAQs we often get as a lab. Hopefully these help make glycobiology insights more accessible to all!
What role do aberrant sugars play in disease progression?
Aberrant glycosylation—the abnormal addition or modification of sugar molecules on proteins and lipids—represents a universal hallmark of cancer, diabetes, and neurodegenerative disorders. Unlike genetic mutations, these are dynamic post-translational modifications that alter cell signaling, immune recognition, and protein stability in real time. In cancer, changes in N-linked glycans (N-glycans), the mucins, and other types of glycans on the cell surface promote tumor growth, metastasis, and immune evasion. In metabolic disease, dysregulated intracellular O-glycans, notably O-linked N-acetylglucosamine (O-GlcNAc), strongly reduce insulin sensitivity and increase cellular stress responses. The Fehl Lab investigates these alterations not merely as biomarkers, but as functional drivers of disease that can be targeted with chemical precision.
What is the hexosamine biosynthetic pathway (HBP), and why does it matter?
The HBP is a metabolic branch point that converts approximately 2−5% of cellular glucose into UDP--acetylglucosamine (UDP-GlcNAc), the obligate donor substrate for O-GlcNAc transferase (OGT). This pathway serves as a cellular nutrient sensor, integrating signals from glucose, amino acid, fatty acid, and nucleotide metabolism. When dysregulated, excessive HBP flux drives pathological O-GlcNAcylation of transcription factors and metabolic enzymes, contributing to insulin resistance, diabetic complications, and cancer cell proliferation. Understanding HBP flux rates across tissues—from skeletal muscle to pancreatic β-cells—is central to our research on metabolic disease mechanisms.
What chemical tools does the Fehl Lab use to study hexosamines and glycoproteins?
We employ a multifaceted chemical biology toolkit to interrogate glycosylation in living cells:
- Metabolic labeling with bioorthogonal handles: Using azide or alkyne-tagged monosaccharide analogs (see our publication for light-released probes! https://pubmed.ncbi.nlm.nih.gov/35810714/) that are incorporated into glycans and detected via fluorescence and mass spectrometry.
- Chemoenzymatic labeling: We use and develop protein-based systems to tag sugars within specific glycoprotein classes. (see our publication: https://pubmed.ncbi.nlm.nih.gov/35819414/)
- Quantitative mass spectrometry: Proteomics to map site-specific O-GlcNAc occupancy and stoichiometry across the proteome. We also use metabolomics to track specific metabolic pathways!
- Spatially resolved glycomics: Fluorescence imaging of glycan dynamics using reporters and biosensors allows us to use CRISPR gene editing, protein design, and assay development for sensitive nutrient tracking.
These approaches allow us to measure glycoprotein dynamics, functional phenotypes, and sugar-related signaling pathways with quantitative accuracy.
Why is glycoscience critical for the future of medicine?
Despite over half of all human proteins being glycosylated, glycoscience remains underrepresented in the genomic era. Glycans function as the “dark matter” of the proteome—mediating cell-cell communication, pathogen infection, and intracellular signaling. Unlike proteins, glycan structures are not template-encoded, creating vast structural heterogeneity that demands chemical, rather than genetic, tools for manipulation. Advances in glycoscience directly reveal new drug targets and enable next-generation therapeutics for diabetes and cancer.
How does mentoring work in the Fehl Lab?
Mentoring in the Fehl Lab follows a graduated independence model rooted in chemical biology training. We emphasize:
- Technical rigor: Dr. Fehl will work with you to design experiments, analyze your data, and generate publication-quality images and presentations that pass the peer-review process.
- Skills: Hands-on mastery of tissue culture, mass spectrometry, organic synthesis, and quantitative proteomics.
- Critical thinking: Our trainees design experiments to distinguish correlation from causation in glycosylation pathways, often integrating multi-omic datasets from cells, tissue, and even preclinical drug treatment studies in model organisms.
- Career stewardship: Individual development plans tailored to industry (biotech/pharma) or academic trajectories, with explicit training in grant writing, peer review, and scientific communication.
We strongly value inclusive excellence, recognizing that diverse perspectives drive innovation in glycobiology.
Why is the Fehl Lab a great environment for research?
Our laboratory sits at the intersection of chemical biology, proteomics/transcriptomics, and accurate metabolic disease models. Researchers benefit from immediate access to:
- State-of-the-art mass spectrometry facilities for glycoproteomics.
- Collaborative networks spanning chemistry, biology, and clinical medicine.
- A culture that values both mechanistic depth and translational potential. We want to develop new therapies!
We specifically seek trainees interested in bridging basic science discoveries with clinical applications, particularly regarding metabolic disease heterogeneity.
Why choose Wayne State University and Detroit for glycoscience research?
Wayne State University School of Medicine offers an unparalleled translational research environment distinct from traditional academic settings:
World-Class Clinical Access: Our location in Detroit’s Midtown Medical Center places researchers adjacent to the Detroit Medical Center (DMC) and Karmanos Cancer Institute—an NCI-designated Comprehensive Cancer Center. This proximity facilitates rapid translation of glycomic discoveries into clinical trials and patient cohort studies.
Unique Patient Populations: Detroit serves one of the nation’s most diverse and underserved patient populations, offering unique opportunities to study health disparities in metabolic disease and cancer. The prevalence of Type 2 diabetes and obesity in our catchment area provides critical real-world data on aberrant glycosylation in these conditions, particularly among populations historically underrepresented in biomedical research.
Cutting-Edge Sample Access: Through partnerships and our many collaborators at the iBio Diabetes Clinic (Integrated Biosciences Center) and the Karmanos Cancer Institute, we have access to valuable biomedical samples. Our goal is to help PEOPLE, and Detroit is an excellent place to be for that goal.