Research Interests
Developmental Epigenetics
Epigenetics is an exciting field that impacts basic biomedical research and clinical medicine. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs provide dynamic, heritable and reversible ways of modulating genome function. They affect a number of processes such as chromosome architecture, chromatin function and gene expression.
We are interested in understanding how epigenetic mechanisms regulate gene activity and how they respond to environmental cues (e.g. nutrition), with a focus on imprinted genes and developmental pathways that link growth with metabolic function.
The work in the lab is divided into three areas:
1- Epigenetics, growth and metabolism
Genomic imprinting is a form of epigenetic regulation in mammals which results in the silencing of one of the two gene copies, according to parental origin. Imprinted genes play key roles in maternal allocation of resources that affect the development of the placenta, fetal and infant growth, glucose and fat metabolism as well as adult behaviours. We are studying how imprinted genes, and more generally epigenetic modifiers, control developmental growth and metabolism, using genetically engineered mouse models, in vivo physiological assays, and cell-based systems.
2- Epigenetics and gene-environment interactions
Epigenetics underpins interactions between the genome and the environment. Environmentally induced changes to the epigenome that may occur during the “waves” of genome-wide epigenetic reprogramming in early development are likely to have long term health consequences. We aim at finding key genes that, when epigenetically de-regulated by sub-optimal nutrition in early development, may contribute to onset and risk of diabetes and obesity phenotypes in later life. We use a combination of (epi)genomic-wide screens and in vitro manipulation of epigenetic machinery, in rodent and human biological materials, to detect loss of epigenetic cellular memory and its consequences.
3- Inter-organ communication during pregnancy and lactation
A key question in reproductive endocrinology that remains largely unanswered is the nature of placental signals that travel to distant maternal and fetal organs and the roles that they play in the developmental physiology of organ targets. We are using novel transgenic tools to decipher the complex signalling that occur at the maternal-fetal-infant interface by labelling placental derived proteins with biotin and follow their ‘homing’ into key metabolic organs. We are particularly interested in unravelling new mechanistic principles of insulin resistance in pregnancy using mouse models of impaired endocrine placental output.
Group Members
Dr. Ionel Sandovici, Senior Research Associate
Cherlyn Tan, PhD student (with Dr. Russell Hamilton)
Tiago Morais, PhD student (with Prof. Mariana Monteiro)
Zhu Hongyu, MPhil student
