Research Interests
The aim of our research is to find out how obesity and gestational diabetes during pregnancy alters development of the baby’s hypothalamus- an area of the brain that is essential for regulating food intake. Research from our group and others shows that obesity and gestational diabetes in pregnancy disrupt the normal development of the hypothalamus, which means it cannot correctly regulate food intake to maintain energy homeostasis. We have shown in rodent models this leads to increased food intake, and we believe this is a major contributor to the increased obesity rates seen in the children of women who have obesity. During pregnancy, the mother’s hypothalamus undergoes lots of changes and rewiring. We are also interested in what the signals are for these changes, and whether obesity and gestational diabetes in pregnancy alter the natural changes that occur in the mother’s brain during pregnancy.
Our research is addressing important gaps in our knowledge of how obesity during pregnancy affects the long- term metabolic health of the offspring and the mother. Our research can be divided into 3 main themes:
- The role of insulin in mediating the effects of obesity in pregnancy on offspring hypothalamic development - We are using animal and cellular models to learn more about the molecular mechanisms that mediate the effects of maternal obesity on offspring hypothalamic development and function. If we understand the mechanisms at play during a pregnancy with obesity and gestational diabetes, we can try and intervene to stop the inter-generational transmission of obesity risk. We are particularly interested in the role of insulin, as this is one of the main factors altered in both the mother and baby during a pregnancy complicated by obesity. We are using mouse models to define how the increased insulin levels in a pregnancy with obesity alters hypothalamic development in the baby.
- Developing clinically relevant intervention strategies to limit the impact of obesity and gestational diabetes on the offspring’s brain and long-term metabolic health - It is currently not feasible to ensure all women enter pregnancy with a healthy BMI, so interventions to improve the health of offspring exposed to obesity in pregnancy may need to occur during pregnancy or even after birth. An understanding of the mechanisms at play during pregnancy will enable us to a) better advise individuals who have obesity or gestational diabetes during pregnancy and b) develop intervention strategies to stop the inter-generational transmission of obesity risk. We are investigating whether lifestyle interventions (such as increased exercise) can rescue the changes we see in the baby’s brain in pregnancies complicated by obesity. We are also interested in drugs that lower the mother’s glucose and insulin levels (such as metformin) and that can help the mother to achieve a lower body weight (such as semaglutide and tirzepatide).
- Understanding how the placenta communicates with the maternal brain and if this communication is required for maternal neuronal adaptations in pregnancy. - During pregnancy the maternal brain undergoes significant rewiring in order to make sure enough nutrition reaches the growing baby, to store fuel reserves ready for lactation, and to enable behavioural changes to prepare to care for the baby. We believe the placenta (which is attached to the baby) releases signals which travel to the mother’s brain to tell the hypothalamus to make these changes. With our collaborators Professor Sue Ozanne, Professor Miguel Constancia and Professor Carlos Guardia (NIH) we are investigating these mechanisms and whether they are disrupted in pregnancies where the mother has obesity or gestational diabetes.
Research Funding
EU Horizon (MCSF to Dr Matt Higgins)
Awards
I hold a Dorothy Hodgkin Fellowship from the Royal Society.
I was awarded the 2023 Rank prize New Lecturer Award in Nutrition.
I previously held a Sir Henry Wellcome Post-doctoral Fellowship (2015-2020).
Group Members
Wai Ping (L) Wong, Senior research technician - wpw30 at medschl.cam.ac.uk
Wanlin (Susan) Sun, PhD student - ws441 at cam.ac.uk
Rosanne Chong, post doc - ps993 at cam.ac.uk
Matt Higgins, MSCA Postdoctoral Fellow - mh2351 at cam.ac.uk
Keyshla Negron, NIH Oxcam PhD student joint with Prof Susan Ozanne (IMS) and Prof Carlos Guardia (NIH)
