The OVS lab overall goal is to study the impact of sweets during various period of development and diseases.
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 7,000 human proteins modified 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 the lab is interested in understanding the impact of Non-Nutritive Sweeteners (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, gut dysbiosis and increase toxicity. Nevertheless, the fundamental mechanisms of those changes are far from understood. Therefore, we aim to understand the impact of NNS on detoxification and and proper placental protective role.
O-GlcNAcylation cycling in Pituitary Adenoma
Each year, there are approximately 10,000 new pituitary adenoma diagnoses is the US alone, with approximately 5,000 surgeries occurring annually for the resection of these tumors and annual surgical costs may reach $100 million. on the other hand, O-GlcNAcylation has been studied extensively in cancer development. indeed, increase of O-GlcNAcylation level is associated with cancer onset and many oncogene and tumor suppressor are regulated by O-GlcNAc modification. Therefore, we aim to study the impact of O-GlcNAc cycling in the development of pituitary adenoma.
Placenta and O-GlcNAcylation in Gestational Diabetes
Worldwide, Gestational Diabetes Mellitus (GDM) is surging, driving the need of a better understanding of drivers and molecular mechanisms to prevent short and long-term consequences of GDM on mothers and babies. In this context, studying the role of nutrient-sensing modification, such as O-GlcNAcylation, of proteins is highly significant to tie environmental influences on GDM development and explore new prognostic and, potentially therapeutic, options. We are particularly fascinated in the fact that NSM can regulate placental hormones, involved in GDM onset, as well as explain the difference in clinical presentations based on fetal sex, potentially leading to new prognostics protocols to assist post-partum clinical care.