Research
Mounting evidence suggests that poor nutrition (e.g. folate deficiency) can influence our epigenomes leading to increased disease risk in adult life and in the next generation. Understanding how diseases are epigenetically transmitted between generations will impact human health; however, the mechanism remains unclear. To explore this phenomenon, I will utilise a genetic mouse line (Mtrr) in which normal folate metabolism is disrupted resulting in congenital defects similar to those seen in maternal folate deficiency in humans. Remarkably, the phenotypes in the Mtrr model, such as growth restriction, developmental delay and congenital defects (e.g. neural tube, heart and placental defects) are transgenerationally inherited by the wildtype grandprogeny. Using genetic, cellular and embryo manipulation techniques in the Mtrr model, I will investigate the transgenerational effects of folate metabolism on feto-placental development,
which may change how we think about disease inheritance.
Publications
1) Rakoczy J, Zhang Z, Bowling FG, Dawson PA, Simmons DG.”Loss of the sulfate transporter Slc13a4 in placenta causes severe fetal abnormalities and death in mice.”Cell Res. 2015, 25(11):1273-6
2) Rakoczy J, Lee S, Weerasekera SJ, Simmons DG, Dawson PA. “Placental and fetal cysteine dioxygenase gene expression in mouse gestation.” Placenta.
2015, 36(8):956-9
3) Rakoczy J, Fernandez-Valverde SL, Glazov EA, Wainwright EN, Sato T, Takada S, Combes AN, Korbie DJ, Miller D, Grimmond SM, Little MH, Asahara H, Mattick JS, Taft RJ, Wilhelm D. “MicroRNAs-140-5p/140-3p modulate Leydig cell numbers in the developing mouse testis.” Biol Reprod. 2013, 6;88(6):143
