Major Areas of Research
- Role of NK cells in pregnancy
- Regulation of NK cell activation by HLA-peptide complexes
We are interested in the function of NK cells during early pregnancy. Our work has revealed a new, beneficial role of NK cells, which respond to fetal soluble HLA-G by promoting the vascular remodeling required for proper blood supply to the fetus. We have uncovered an endosomal signaling pathway, initiated by an endosome-resident receptor, which endows NK cells with the capacity to promote vascular remodeling. Our work has identified cellular senescence as the molecular mechanism by which this NK-cell response is initiated and sustained. This has exciting implications for NK-cell function at sites of HLA-G expression, such as vascular remodeling at the implantation site during early pregnancy and at the site of HLA-G-expressing tumor cells. The concept that specific signals from NK cells may promote vascular growth and remodeling is new in the field.
Dr. Rajagopalan received her Ph.D. in immunology from the Tufts University School of Medicine in 1991. After postdoctoral research with Dr. Michael Brenner at the Brigham and Womens Hospital, Harvard Medical School, she joined the Laboratory of Immunogenetics in 1994 as a senior staff fellow. She has continued her research in LIG as a staff scientist since 2001.
Rajagopalan S, Long EO. Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20596-601.
Rajagopalan S, Long EO. KIR2DL4 (CD158d): An activation receptor for HLA-G. Front Immunol. 2012;3:258.
Rajagopalan S. Endosomal signaling and a novel pathway defined by the natural killer receptor KIR2DL4 (CD158d). Traffic. 2010 Nov;11(11):1381-90.
Rajagopalan S, Long EO. Antagonizing inhibition gets NK cells going. Proc Natl Acad Sci U S A.2010 Jun 8;107(23):10333-4.
Rajagopalan S, Moyle MW, Joosten I, Long EO. DNA-PKcs controls an endosomal signaling pathway for a proinflammatory response by natural killer cells. Sci Signaling. 2010 Feb 23;3(110):ra14.
Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, van der Meer A, Joosten I, Long EO. Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol. 2006 Jan;4(1):e9.