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Irving Aye

Irving  Aye

2018 Next Generation Fellow


Research Interests

My current research focuses on the role of placental metabolism in mediating sex-specific responses during pre-eclampsia and fetal growth restriction. I am testing the hypothesis that genes which escape X-chromosome inactivation specifically in the placenta mediate sex-differences in placental function with consequences on adverse fetal outcomes. An additional area of my research is the use of lentiviral vectors to perform placental-specific gene manipulation (overexpression or deletion) in mice. A key feature of my research is the combination of a variety of models including primary human cells and rodent models, and the use of clinical human samples to answer questions of biological and clinical significance.

Key Publications

Gong S*, Sovio U*, Aye ILMH*, Gaccioli F*, Dopierala J, Johnson MD, Wood AM, Cook E, Jenkins  BJ, Koulman A, Casero Jr. RA, Constancia M, Charnock-Jones DS, Smith GCS. Placental polyamine metabolism differs by fetal sex, fetal growth restriction and preeclampsia. JCI Insight. 2018; 3(13): e120723. (*equal contribution)

 

Aye ILMH, Moraitis AA, Stanislaus D, Charnock-Jones DS, Smith GCS. Retosiban prevents stretch-induced human myometrial contractility and delays labor in Cynomolgus monkeys.  J Clin Endocrinol Metab. 2018; 103(3): 1056-1067.

 

Aye IL†, Rosario FJ, Powell TL, Jansson T. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc Natl Acad Sci U S A. 2015; 112(41):12858-12863. (†corresponding author)

 

Aye IL†, Jansson T, Powell TL. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling. Physiol Rep. 2015; 3(10):e12594. (†corresponding author)

 

Aye IL*†, Lager S*, Ramirez VI, Gaccioli F, Dudley DJ, Jansson T, Powell TL. Increasing maternal BMI is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways. Biol Reprod. 2014; 90(6):129. (*equal contribution, †corresponding author).

 

Aye IL†, Gao X, Weintraub S, Jansson T, Powell TL. Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis. Mol Endocrinol. 2014; 28 (4):512-524. (†corresponding author)

 

Aye IL†, Jansson T, Powell TL. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated System A amino acid transport in primary human trophoblasts. Mol Cell Endocrinol. 2013; 381 (1-2):46-55. (†corresponding author)

 

Aye IL and Keelan JA. Placental ABC transporters, cellular toxicity and stress in pregnancy.

Chem Biol Interact. 2013; 203 (2):456-466.

 

Aye IL, Powell TL, Jansson T. Adiponectin – The missing link between maternal adiposity, placental transport and fetal growth? Placenta. 2013; 34 (Suppl A):S40-S45.

 

Aye IL†, Waddell BJ, Mark PJ and Keelan JA. Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF-kappaB.

Mol Hum Reprod. 2012;18(7):341-53. (†corresponding author)

 

Aye IL, Waddell BJ, Mark PJ and Keelan JA. Oxysterols inhibit differentiation and fusion of term primary trophoblasts by activating liver X receptors. Placenta. 2011;32(2):183-91.

 

Aye IL, Waddell BJ, Mark PJ and Keelan JA. Placental ABCA1 and ABCG1 transporters efflux cholesterol and protect trophoblasts from oxysterol induced toxicity. Biochim Biophys Acta. 2010;1801(9):1013-24.

 

Aye IL, Singh AT and Keelan JA. Transport of lipids by ABC proteins: interactions and implications for cellular toxicity, viability and function. Chem Biol Interact. 2009;180(3):327-39.

 

Aye IL, Paxton JW, Evseenko DA and Keelan JA. Expression, localisation and activity of ATP binding cassette (ABC) family of drug transporters in human amnion membranes.

Placenta. 2007;28(8-9):868-77.

 

Pubmed link to bibliography: https://tinyurl.com/y8bw9bsx

 

Book Chapter

Irving L.M.H. Aye, Susanne Lager, Theresa L. Powell, Chapter 6: The role of placental inflammasomes in linking the adverse effects of maternal obesity on fetal development. In: Metabolic Syndrome and Complications of Pregnancy. Enrico M. Ferrazzi & Barry Sears (Editors). Springer Press.