Research Interests:
Understanding the Impact of Early Life Nutritional Exposures on Long-term Cardiometabolic Health:
The major focus of our research is to understand the mechanisms by which sub-optimal early life nutrition impacts on long-term risk of type 2 diabetes, obesity, cardiovascular disease and premature death. A large number of epidemiological studies suggest that such relationships exist- for example of children born from obese pregnancies or those exposed to under-nutrition in utero- however the molecular mechanisms mediating such relationships are not well understood. Our goal is to define these mechanisms and to use this understanding to develop rational prevention and intervention strategies. Our most recent work has focussed on applying our mechanistic understanding to address the most appropriate interventions during obese, diabetic pregnancy for maximum short- and long- term benefit to both mother and child.
Maternal-Fetal Communication during Health and Complicated Pregnancy:
The placenta is an endocrine organ that acts as a key interface between mother and fetus with the capacity to influence immediate and long-term maternal and offspring metabolism. We have shown that its structure and function is modulated in obese diabetic pregnancies and responsive to both pharmacological (e.g. metformin) and lifestyle (e.g. physical activity) interventions during pregnancy. Our current studies are utilising mouse models and isolated human trophoblasts to identify secreted placental proteins (some of which are in extracellular vesicles) that traffic to maternal and fetal organs to influence their function and to establish how this is modified during complicated pregnancies.
Interventions During Obese Glucose Intolerant Pregnancy to Improve Maternal and Offspring Cardio-Metabolic Health:
Pregnancy is a window of opportunity to improve the health of at least two generation. However, it is also a complex challenge with short and long- term effects on two individuals – mother and child to be considered. We have developed models of both pharmocological (administration of metformin) and lifestyle (peri-gestational exercise) interventions during obese pregnancy. These intervention studies are providing vital clues as to the mechanism underlying the programming of offspring cardio-metabolic disorders in maternal obesity. Our findings from studies with metformin administration during pregnancy have highlighted beneficial immediate effects on maternal physiology but identified some potential negative effects on maternal metabolism. On-going studies are exploring the mechanisms underlying these effects.
miRNAs as mediators of early life nutrition on long term health:
We have a strong interest in defining the role of miRNAs as potential mediators of the effects of early life nutrition on gene expression and organ function. We use a range of molecular techniques to determine whether microRNAs in tissues such as the brain, heart, liver and adipose tissue may be epigenetic regulators that are sensitive to programming by the nutritional environment associated with obese diabetic pregnancies and thus contribute to the dysfunction observed in these tissues. Some of our current work is focussed on understanding if alteration in miRNA content of extracellular vesicles is one mechanism by which sub-optimal early life nutrition impacts on inter-organ communication.
Early Life Nutrition, Oxidative Stress and Accelerated Ageing:
One of the striking observations in offspring exposed to sub-optimal early life nutrition has been that life span can be increased or decreased by restricting growth either during suckling or fetal life, respectively. This led us to hypothesise that accelerated cellular ageing may be one mechanism by which sub-optimal early life nutrition increases risk of traditionally adult-onset diseases such as type 2 diabetes and cardiovascular disease. We subsequently showed that programmed differences in lifespan are associated with differences in telomere length, mitochondrial function and oxidative damage in a number of organs. We are currently exploring if accelerated ageing is a common mechanism linking the effects of a range of sub-optimal nutritional exposures on long-term cardiometabolic health.
Group Members
Miss Andreea Cristian, PhD Student - adc90 at medschl.cam.ac.uk
Mrs Claire Custance, Senior Research Technician - cg358 at cam.ac.uk
Dr Adriana Paz Cordova, Post-doctoral Research Fellow - ap2427 at medschl.cam.ac.uk
Dr Denise Fernandez-Twinn, Senior Research Associate - df220 at cam.ac.uk
Pedro Moniz Gomes, MPhil Student - pm861 at cam.ac.uk
Keyshla Negron, NIH Oxcam PhD student joint with Dr Laura Dearden (IMS) and Prof Carlos Guardia (NIH) - kn447 at cam.ac.uk
Dr Lais Vales Mennetti, Postdoctoral Research Associate - lv325 at medschl.cam.ac.uk
Mrs Elaine Withers, Personal Assistant - ew439 at medschl.cam.ac.uk
Kwun Kiu (Will) Wong, Senior Research Technician/Lab Manager - kkw28 at medschl.cam.ac.uk
