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Meghna Ramesh

Research Interests

Research summary

NK cells are generally thought of as effectors cells of innate immunity, where they kill cancer cells and virally infected cells. The NK cells in the uterus (Uterine NK cells, uNK) are phenotypically and functionally different from those present in peripheral circulation. They are present prior and during pregnancy and predominate over other lymphocytes during the initiation of invasive placentation in both human and mouse. Their exact function in pregnancy is unknown, but increasing evidence points to a role in co-ordinating the transformation of uterine spiral arteries. In women, inadequate changes in the spiral arteries are associated with severe complications of pregnancy, including pre-eclampsia, fetal growth restriction and recurrent miscarriage. 
Recently, our laboratory has made the discovery of an un-conventional subset of NK cells that is retrieved at different sub-compartments of the mouse uterus, prior and during gestation (E10.5). On the other hand, using mutant mice, we have identified which subset is necessary for spiral arteries remodeling and fetal growth

The aim of this project is to investigate further the dynamic distribution of different uNK cell subsets at different gestation stages in the murine model. One NK cells subset has been identified to be critical for fetal growth by Dr Selma Boulenouar (manuscript in preparation).

 

Funding:

  1. LUF International Study Fund
  2. Minerva Scholarship Fund
  3. Erasmus + for Traineeships
  4. Leiden University Outbound Study Grant
  5. Jo Keur Fund

Key Publications

  1. MHC-dependent inhibition of uterine NK cells impedes fetal growth and decidual vascular remodelling. Kieckbusch J, Gaynor LM, Moffett A, Colucci F. Nat Commun. 2014 Feb 28;5:3359.
  2. Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, Bauer J, Hiby SE, Colucci F, Moffett A. J Clin Invest. 2013 Oct 1;123(10):4264-72.
  3. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4012-7. COMMENT BY A. ERLEBACHER: Strangers no more: uterine NK cell recognition of the placenta in mice.