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Erica Watson

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University Lecturer in Reproductive Biology
Tel: +44 (0)1223 333858 (office), +44 (0)1223 746744 (lab), Fax: +44 (0)1223 333840, E-mail: edw23@cam.ac.uk

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.

I am pleased to consider enquiries from prospective PhD students and postdocs. Please contact me by email in the first instance.

Current lab members
Maria Bruni (Graduate Student)
Nisha Padmanabhan (Graduate Student)
Xander Anderson (Senior Research Technician)

Former lab members
Grace Petkovic (Research Technician, former PDN Part II student)
Hajera Begum (Summer student)
Jeny Cherukad (Summer student and PDN Part II student)
Verity Evans [nee Wainwright] (PDN Part II student)

Main Collaborators
Prof Anne Ferguson-Smith (Dept Genetics, University of Cambridge)
Prof Bill Colledge (Dept PDN, University of Cambridge)
Prof Dino Giussani (Dept PDN, University of Cambridge)
Prof Graham Burton and Dr Hong Wa Yung (Dept PDN, University of Cambridge)
Dr Francesco Colucci and Dr Selma Boulenouar (Dept Obstetrics & Gynaecology, University of Cambridge)

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

Padmanabhan N and 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 and 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. *Equal contribution.

Roseboom TJ and 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 and 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 and 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 and 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 and 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 and Cross JC (2005) Development of structures and transport functions in the mouse placenta. Physiology 20(3): 180-93.

To download my complete publication list in PDF format, please click here or see a linked version on ResearchGate.

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Mouse embryo developing over time Using a light microscope, we generated this image showing the growth and development of a mouse embryo during the second week of pregnancy. The first embryo is nine days old and has few recognizable features whereas the last embryos is fourteen days old and more closely resembles a mouse pup as birth.


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Transgenerational epigenetic effects of folate metabolism This video abstract outlines the seminal work in our lab. It explains that genetic deficiency in folate metabolism in maternal grandparents affects development of their wildtype grandprogeny, even if the mothers are also wildtype. See Padmanabhan et al, 2013 (Cell) for more details.


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Mtrr deficiency affects development two generations later Mtrrgt mutation in either maternal grandparent results in intrauterine growth restriction, developmental delay, and congenital abnormalities (e.g., heart, placental and neural tube defects) in their genetically wildtype grandprogeny.