University of Cambridge
Tennis Court Road
The question we are addressing is: how does the maternal immune system regulate placentation in humans? Our view of the fetal allograft is one of cooperation between mother and fetus. We focus on how the dominant population of uterine leukocytes, Natural Killer (NK) cells, that have receptors for HLA class I ligands on fetal trophoblast cells, regulate trophoblast function.
We work in close collaboration with Dr Francesco Colucci in the Department of Obstetrics and Gynaecology.
The main areas of current research are:
1) Interactions between maternal Killer-cell Immunoglobulin-like Receptor (KIR) and fetal HLA-C molecules. Because both KIR and HLA-C genes are highly polymorphic, each pregnancy is likely to be different. Our genetic and functional studies in Europeans and Africans show certain KIR/HLA-C genetic combinations are associated with extremes of the normal birth weight distribution.
2) Culture of human trophoblast cells. Studies on pregnancy disorders are limited because trophoblast stem cell lines have not been obtained. We are working to identify, isolate and culture trophoblast cells from early pregnancy.
3) Maternal Health Research Unit linked to Makerere University, Mulago Hospital, Kampala, Uganda. After the success of our initial project studying Immunogenetics of KIR/HLA-C variants linked to pre-eclampsia in Ugandans, we are now extending the link to investigate puerperal sepsis and obstructed labour. I lead the maternal health theme as part of the Wellcome Trust Centre for Global Health Research.
Principal Investigator: Ashley Moffett
Associate Lecturer: Andrew Sharkey
Lab Manager: Lucy Gardner
Research Fellows: Olympe Chazara
Post Doc: Selma Boulenouar
Senior Technician: Lydia Farrell
Mulago Hospital Annettee Nakimuli
Nakimuli A, Chazara O, Farrell L, Nemat-Gorgani N, Norman PJ, Tukwasibwe S, Jayaraman J, Traherne JA, Lougee E, Vaughan RW, Elliott AM, Byamugisha J, Kaleebu P, Mirembe F, Parham P, Hiby SE, Moffett A. (2015)
A KIR B centromeric region found in Africans but not Europeans is protective against pre-eclampsia.
PNAS doi: 10.1073/pnas.1413453112
Moffett A, Shreeve N. (2015)
First do no harm: uterine natural killer (NK) cells in assisted reproduction.
Human Reproduction May 7 pii: dev098. [Epub ahead of print]
Hiby SE, Apps R, Chazara O, Farrell LE, Magnus P, Trogstad L, Gjessing HK, Carrington M, Moffett A. (2014)
Maternal KIR in Combination with Paternal HLA-C2 Regulate Human Birth Weight.
J Immunol. Jun 1;192(11):5069-73.
doi: 10.4049/jimmunol.1400577. PMID: 24778445
Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, Bauer J, Hiby SE, Colucci F, Moffett A (2013)
Maternal uterine NK cell–activating receptor KIR2DS1 enhances placentation
Journal of Clinical Investigation. doi:10.1172/JCI68991.
Parham P, Moffett A (2013)
Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.
Nat Rev Immunol 13:133.