Chad E. Slawson, PhD

Professional Background

Dr. Slawson's laboratory is focused on how O-GlcNAcylation regulates growth and development. Dr. Slawson started working on O-GlcNAc in graduate school in the laboratory of Robert Potter at the University of South Florida, and then he continued his focus on O-GlcNAc in the laboratory of Gerald Hart, discoverer of the modification, at the Johns Hopkins University School of Medicine. Since starting his lab at KUMC in 2011, Dr. Slawson has published papers in the role of O-GlcNAc in cancer, metabolic regulation, transcription, and immune response. He is currently funded by the NIH, Midwest Cancer Alliance, and the Patton Trust.

• BS, Biochemistry, Indiana University
• PhD, Biochemistry, Univ. of South Florida
• Post Doctoral Fellowship, Biochemistry, The Johns Hopkins School of Medicine, Baltimore, MD

• American Society of Biochemistry and Molecular Biology, co-organizer, 2018 - Present
• National Institute of Health, Membrane Biology and Protein Processing, Ad-Hoc Member, 2018 - 2018
• American Chemical Society, Member, 2007 - Present
• American Society of Biochemistry and Molecular Biology, Member, 2005 - Present

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Research

Overview

What is O-GlcNAc? O-GlcNAc is the addition of a single N-acetyl-glucosamine residue to serine/threonine residues of proteins found in the cytoplasm, nucleus, or mitochondria (O-GlcNAcylation). Unlike extracellular glycosylation, the sugar residue is not elongated into complex oligosaccharides and is added or removed dynamically in response to cellular stimuli by a single O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) respectively. O-GlcNAc is involved in many cellular processes such as nutrient sensing, stress response, transcription, translation, cell signaling, and cell cycle regulation.

O-GlcNAc Regulates Mitochondrial Function: Virtually every cell in a multi-cellular organism requires mitochondria to generate ATP or metabolic precursors; unfortunately, alteration of mitochondrial function is synonymous with diseases like Alzheimer’s disease and Cancer. Post-translationalmodifications (PTM) provide mitochondrial proteins with the molecular diversity needed to respond rapidly to changing environmental conditions. The O-GlcNAc post-translational modification regulates mitochondrial function. Alterations in the expression of OGT or OGA have a profound effect on mitochondrial function. We demonstrated that the expression of mitochondrial nuclear encoded genes is dramatically altered when OGT or OGA is over-expressed. Importantly, these changes lowered electron transport chain function and flux through the TCA cycle. Furthermore, we then demonstrated that mitochondrial generation of reactive oxygen species (ROS) is controlled by O-GlcNAc. Together, our data highlights the role of O-GlcNAc in controlling mitochondrial function during times of nutrient excess or stress.

O-GlcNAc Regulates Transcription: Not surprisingly, O-GlcNAc is a key regulator of gene transcription. O-GlcNAc plays a pivotal role in regulating the human g-globin genes by organizing chromatin-remodeling complexes. One mode of g-globin silencing occurs at the GATA binding sites located at -566 or -567 relative to the ^Ag-globin or ^Gg-globin CAP sites respectively, and is mediated through the DNA binding moiety of GATA-1 and its recruitment of co-repressor partners, FOG-1 and CHD4 (NuRD complex). Both OGT and OGA associate with the g-globin promoter and alterations in the rate of O-GlcNAc addition and removal control expression of the g-globin. These gene expression changes are mediated by changes in the O-GlcNAcylation status of CHD4. Currently, we are developing novel CRISPR based tools to determine the function of OGT and OGA at cis-regulatory elements within the genome.

• O-GLCNAC HOMEOSTASIS REGULATES MITOCHONDRIAL FUNCTION IN ALZHEIMER'S DISEASE, NIH, PI

• Zhang, Z, Parker, M., P, Graw, S, Novikova, L., V, Fedosyuk, H, Fontes, J., D, Koestler, D., C, Peterson, K., R, Slawson, C. 2019. O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis.. The Journal of biological chemistry, 294 (4), 1363-1379
• Zhou, L., T, Romar, R, Pavone, M., E, Soriano-Úbeda, C, Zhang, J, Slawson, C, Duncan, F., E. 2019. Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.. Molecular reproduction and development
• de Queiroz, R., M, Madan, R, Chien, J, Dias, W., B, Slawson, C. 2016. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.. The Journal of biological chemistry, 291 (36), 18897-914
• Tan, E., P, McGreal, S., R, Graw, S, Tessman, R, Koppel, S., J, Dhakal, P, Zhang, Z, Machacek, M, Zachara, N., E, Koestler, D., C, Peterson, K., R, Thyfault, J., P, Swerdlow, R., H, Krishnamurthy, P, DiTacchio, L, Apte, U, Slawson, C. 2017. Sustained O-GlcNAcylation reprograms mitochondrial function to regulate energy metabolism.. The Journal of biological chemistry, 292 (36), 14940-14962
• Machacek, Miranda, Saunders, Harmony , Zhang, Zhen , Tan, Ee Phie, Li, J., Li, Tiangang, Villar, Maira, Artigues, Antonio, Lydic, Todd, Cork, Gentry, Slawson, Chad, Fields, Patrick. 2019. Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment. Journal of Biological Chemistry (294), 8973-8990