These are the fields we are currently working on:
1) Implication of placental galectin-glycan signaling networks for pregnancy outcome
The placenta is the least understood organ and arguably one of the more important, not only for the health of a woman and her foetus during pregnancy but also for the lifelong health of both. Placental structure and function affect the health of the mother, as seen in the development of insulin resistance and of Preeclampsia (PE), gestational hypertension.
Our research group is pioneer in deciphering the role of galectins during pregnancy. We described that dysregulation of galectin-1 (gal-1) is associated with inflammation, faulty placental angiogenesis and subsequent PE development.
Our findings suggest that dysregulation of gal-1 signalling observed in our mouse models during PE development is also clinically relevant for human patients.
Our research answered the initial question of what are the downstream mechanism striggered by galectins during gestation. Now, we seek to answer a more complex question which is related to the upstream pathways that influence galectin actions in pregnancy. Thus, we aim to examine the placental GLYCOCODE, which is interpreted by galectins, in order toidentify sugar-based interactions in the placental niche that relate to both health and preeclampsia disease.
2) Galectins in cardiovascular disease associated with pregnancy disorders
Pregnancy is a “stress test” for lifelong maternal health; placental function may be both a markerand a predominant cause of future cardiovascular disease (CVD). The role of galectins in the development of CVD has raised a great deal of attention. Galectins have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis.
Although the correlation between pregnancy disorders (such as Preeclampsia) and future CVD is proven, many pathophysiological aspects remain unclear. Both diseases share many risk factors and features including hyperlipidaemia, obesity, hypertension, endothelial dysfunction, and lipid deposition in vessel walls. Most cardiovascular research has focused on CVD late in life, and little attention has been paid to the mechanism accounting for the increased risk of women with pregnancy complications and their offspring.
This research topic has the overarching goal of dissecting the galectin signature (comprising several family members) that contributes to extrinsic and intrinsic factors to promote placenta insufficiency and subsequently CVD development.
3) SWEETTALK: Maternal-to-Placental Communication in pregnancies complicated with metabolic disorders.
Gestational Diabetes (GDM) occurs when a woman without diabetes develops hyperglycaemia during pregnancy. It is the commonest medical disorder of pregnancy affecting between 5-18% of all pregnancies and a major concern because of the impact it has on fetal growth (e.g. infants born large for gestational age (LGA), increased risk of preterm and instrumental delivery, caesarean section and stillbirth).
The placenta is essential for normal fetal metabolism and growth and during hyperglycaemia, there are numerous alterations that occur, including low-grade inflammation, changes to the placental vasculature, rates of growth and the organ’s ability to transfer nutrients to the fetus; these changes are all also associated with increased- or decreased- fetal growth.
Carbohydrate-dependent interactions are critical in processes associated with health pregnancy as well as in pathological disorders, most notably in GDM. During pregnancy, such carbohydrate-dependent interactions are mediated in a large part by galectins, a family of soluble proteins that interact with N-acetyllactosamine (LacNAc) epitopes. Galectins are now established as key regulators of fundamental pregnancy processes including metabolism, placentation and inflammation.
In collaboration with Prof. Karen Forbes (University of Leeds, UK) we aim to understand the maternal to placental communication taking in account the glycoimmunology interactions during metabolic pregnancy disorders.