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Dr Erica D Watson

Dr Erica D Watson

Lecturer in Reproductive Biology

Lister Research Prize Fellow

Erica Watson is accepting applications for PhD students.

Office Phone: +44 (0) 1223 333858, Lab: +44 (0) 1223 746744

Research Interests

Epigenetic changes accrued in the genome throughout one’s lifetime can contribute to an increased risk for disease. These changes may occur through exposure to environmental stressors (e.g., toxins, nutrient deficiency, etc.) that alter epigenetic factors, such as patterns of DNA methylation, ultimately causing gene misexpression. Exposure to these environmental factors in utero may alter epigenetic programming, such that the nine months before you are born may have a profound impact on your health later in life. Mounting evidence also indicates that maternal, paternal or even grandparental exposure may contribute to congenital malformations and/or metabolic and cardiovascular diseases in children and grandchildren. This non-conventional inheritance occurs via epigenetic rather than genetic inheritance, and implicates the germline. Very little is understood regarding transgenerational mechanisms of inheritance. Our aim is to explore how developmental abnormalities and disease risk is epigenetically transmitted between generations. Further understanding this mechanism will drastically impact human health.

Transgenerational epigenetic effects of folate metabolism

My group currently explores the mechanisms behind the transgenerational epigenetic effects of folate metabolism during fetal and placental development. Folate is a vitamin important for the one-carbon metabolism and methylation of cell components (e.g., DNA). To study this, we use a genetic mouse model with a mutation in a key gene involved in folate metabolism (Mtrrgt) that disrupts folate metabolism and results in similar metabolic effects as human folate deficiency. We recently showed using highly controlled genetic pedigrees that when either maternal grandparent carried the Mtrrgt mutant allele, it was sufficient to cause developmental abnormalities and epigenetic instability in their grandprogeny at midgestation (Padmanabhan et al, 2013 Cell). This occurred even when the mother and the grandprogeny are genetically wildtype for the Mtrr mutation. Some of the abnormalities (e.g., neural tube, heart and placental defects) persisted after embryo transfer experiments and for up to 5 generations, implicating epigenetic inheritance as a mechanism.

Our research goal is to use the Mtrr mouse model to understand the mechanism behind the transgenerational effects of folate metabolism on development by breaking it down into the specific properties of each generation (i.e., grandparental, maternal and placental/embryonic effects) using epigenetic, molecular and embryo manipulation techniques. Ultimately, this will help us explain the role of folate metabolism during development, which has eluded researchers for decades. As well, it will give us clues as to how transgenerational inheritance of disease and phenotypes is achieved.

Key Publications

Padmanabhan N, Jia D, Geary-Joo C, Wu X, Ferguson-Smith AC, Fung E, Bieda M, Snyder FF, Gravel RA, Cross JC, Watson ED, (2013), Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development, Cell, 155(1): 81-93

Padmanabhan N, Watson ED, (2013), Lessons from the one-carbon metabolism: passing it along to the next generation, Reproductive BioMedicine Online, 27(6): 637-43

Colleoni F, Padmanabhan N, Yung HW, Watson ED, Cetin I, Tissot van Patôt MC, Burton GJ, Murray AJ, (2013), Suppression of mitochondrial electron transport chain function in the hypoxic human placenta: a role for miR-210 and protein synthesis inhibition, PLoS ONE, 8(1): e55194

Roseboom TJ, Watson ED, (2012), The next generation of disease risk: are the effects of prenatal nutrition transmitted across generations? Evidence from animal and human studies, Placenta, 33 (Suppl 2): e40-e44

Cherukad J, Wainwright V, Watson ED, (2012), Spatial and temporal expression of folate transporters and metabolic enzymes during mouse placental development, Placenta, 33(5): 440-8

Yung HW, Hemberger M, Watson ED, Senner CE, Jones CP, Kaufmann RJ, Charnock-Jones DS, Burton GJ, (2012), Endoplasmic reticulum stress disrupts placental morphogenesis: implications for human intrauterine growth restriction, Journal of Pathology, 228(4): 554-64

Watson ED, Hughes M, Simmons DG, Natale DR, Sutherland AE, Cross JC, (2011), Cell-cell adhesion defects in Mrj mutant trophoblast cells are associated with failure to pattern the chorion during early placental development, Developmental Dynamics, 240(11): 2505-19

Watson ED, Geary-Joo C, Hughes M, Cross JC, (2007), The Mrj co-chaperone mediates keratin turnover and prevents the formation of toxic inclusion bodies in trophoblast cells of the placenta, Development, 134(9): 1809-17

Watson ED, Cross JC, (2005), Development of structures and transport functions in the mouse placenta, Physiology, 20(3): 180-93

Above: Mouse embryo and placenta at embryonic (E) day 10.5.

Above: Normal mouse embryo development from embryonic (E) day 9.5 to E15.5. Click to enlarge.

Above: Mrj mutant trophoblast stem cells immunostained for keratin 18 (green), actin filaments (red) and DNA (blue). Click to enlarge.

Mouse embryo development over time

Transgenerational epigenetic effects of folate metabolism