91大神

Dr. Olivier-Van Stichelen received her PhD in Biochemistry from the University of Lille, France in 2012, where she studied the nutrient-sensing O-GlcNAcylation in colorectal cancer development. After completing her degree, she was appointed as a post-doctoral Fellow at the National Institute of Health, Bethesda, MD, USA. In this lab, Dr. Olivier-Van Stichelen worked on different aspects of O-GlcNAcylation during development, including X-inactivation of the O-GlcNAc Transferase gene, brain O-GlcNAcase function in mouse KO models and the impact of sugar and artificial sweeteners consumption during pregnancy on the development of metabolic homeostasis.

Dr. Olivier-Van Stichelen established her lab at the 91大神 College of Wisconsin in 2019 at the crossroad of sweeteners, pregnancy, development, and metabolism. Notably, her lab has developed several mouse models for studying O-GlcNAcylation and created the O-GlcNAc database, the reference catalog of O-GlcNAcylated proteins for all species. Some of the current lab projects include studies of (i) O-GlcNAcylation in the pathophysiology of the pituitary gland, (ii) O-GlcNAc transferase’s function in the sexual dimorphism of Gestational Diabetes, and (iii) artificial sweeteners’ impact on detoxification transporters.

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A catalog of O-GlcNAcylated proteins, their O-GlcNAc sites, and corresponding references

Due to the global trend of growing sweetener consumption, determining the interplay between diet and pre- and post-natal development is emerging as a critical area for research. Currently, the average American eats around 22 teaspoons of added sugar every day (30 sugar cubes/day hidden in foods). This modern glucose-rich diet correlates with an increase in the prevalence of obesity, diabetes and others metabolic syndromes. Moreover, the effort to reduce sugar consumption has led people to consume more non-caloric sweeteners (Aspartame, Sucralose, Acesulfame-K...). While they appear healthier for glucose homeostasis than a high carbohydrate diet, recent studies have shown that artificial sweeteners impact glucose metabolism as well as gut microbiota, rising questions about their excessive use.

Therefore, understanding what happens when caloric and non-caloric sweeteners are metabolized is of utmost importance for public health and the focus of my research group.

Nutrient-dependent O-GlcNAc cycling in development and disease

O-GlcNAcylation is one of the key components of diet-responsive signaling. This unique glucose rheostat is a ubiquitous and dynamic glycosylation of intracellular proteins with approximately 1000 modified proteins described to date. Two key enzymes drive O-GlcNAc cycling: The O-GlcNAc transferase (OGT) adds the modification and the O-GlcNAcase (OGA) removes it. Although many studies have focused on the decrease or complete absence of O-GlcNAc cycling by modulating the expression or activity of OGT, only a few studies have targeted hyper-O-GlcNAcylation by disturbing OGA. Because this post-translational modification is directly dependent on glucose input, depleting OGA creates an artificial and constant hyperglycemia-induced O-GlcNAcylation state. Using Oga and Ogt knockout (KO) cellular and mouse models, we can decipher the impact of high carbohydrate diet on embryonic development.

Non-Nutritive Sweeteners in pregnancy and lactation

Part of my lab is interested in understanding the impact of Non-Nutritive Sweetener (NNS) consumption through pregnancy and lactation. Although, NNS have been found in mother’s milk and in placental blood circulation, no study has focused on the fundamental effect of those non-caloric sweeteners on the developing organism. Among the impacts described in adults are changes in intestinal hormonal secretion, glucose metabolism and most fascinating, re- duction of the gut microbiota. Nevertheless, the fundamental mechanisms of those changes are far from understood. Glycoproteins found on the surface of the intestinal epithelium define the glycocalyx and are an essential mammalian mechanism of communication with the gut microbiome. Their reciprocal relationship with the gut microbiome regulates not only nutrient breakdown, and food absorption, but also infection. We are convinced that by altering both microbiome and the detoxification process, NNS exposure in early life will impact metabolic homeostasis later in life.