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Professor Ashley Moffett

Professor Ashley Moffett

Ashley Moffett is interested in taking PhD students.

Ashley Moffett is available for consultancy.


Research Interests

The question we are addressing is that the maternal uterine immune system is crucial in regulating the process of placentation. Specifically, how does the dominant population of uterine leukocytes, Natural Killer cells recognise MHC Class I ligands on fetal trophoblast cells and how might this result in altered trophoblast function. More recently, we have focused on two trophoblast MHC Class I ligands, HLA-G and HLA-C. There is increasing evidence that a major function of the NK receptors that bind HLA-C (known as KIR) are pivotal in determining how far trophoblast penetrates into the uterus. This trophoblast invasion is essential to tap into the maternal blood flow. We have shown that one particular maternal KIR and fetal HLA-C combination is associated with recurrent miscarriage, fetal growth restriction and pre-eclampsia. The impact of the immunological maternal-fetal interaction on low birth weight has far reaching consequences including on adult health.

Keywords

enzyme assays ; immunohistochemistry ; HLA-C ; KIR ; HLA-G ; human studies ; natural killer cells ; pregnancy ; FACS

Topics

  • pre-eclampsia
  • autoimmunity
  • recurrent miscarriage

Key Publications

Male V, Gardner L, Moffett A. Isolation of cells from the feto-maternal interface.Curr Protoc Immunol. 2012 Apr; Chapter 7: Unit 7.40.1-11.

Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M, Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci USA 2011. 108: 4012-4017

Male V, Sharkey A, Masters L, Kennedy PR, Farrell LE, Moffett A.  The effect of pregnancy on the uterine NK cell KIR repertoire. Eur J Immunol. 2011 Oct;41(10):3017-27.

Colucci F, Boulenouar S, Kieckbusch J, Moffett A. How does variability of immune system genes affect placentation? Placenta 2011 32: 539-545

Apps R, Sharkey A, Gardner L, Male V, Trotter M, Miller M, North R, Founds S and Moffett A. Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells. Placenta 2011 Jan;32(1):33-43.

Hiby SE, Apps R, Sharkey AM, Farrell LE, Gardner L, Mulder A, Claas FH, Walker JJ, Redman CC, Morgan L, Tower C, Regan L, Moore GE, Carrington M, Moffett A. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J. Clin. Invest. 2010 120: 4102-4110.

Male V, Hughes T, McClory S, Colucci F, Caligiuri MA, Moffett A (2010). Immature NK cells, capable of producing IL-22, are present in human uterine mucosa. J. Immunol. 185: 3913-3918.

Successful invasion of the placenta into the wall of the uterus is finely balanced.