Work in the Erlebacher laboratory lies at the intersection of immunology and developmental biology. In particular, we are interested in how the developmental properties of a tissue influence its ability to mount a successful immune response, and, conversely, how cells of the immune system influence tissue development and remodeling. The main platform for our research is the mouse uterus. This organ is not only a simple mucosal tissue amendable to extensive experimental manipulation, but its ability to accommodate the presence of immunologically foreign tissues during pregnancy (i.e. the fetus and placenta) provides a striking example of how the anatomical organization and developmental plasticity of a tissue determines its immunological properties. Moreover, reproductive success relies upon the immunological protection afforded the fetus and placenta by the uterus, with insight into how this process breaks down having implications for disorders of human pregnancy, including spontaneous abortion, intrauterine growth restriction, preeclampsia and preterm birth. We also study how the parenchymal cells of the uterus, through their specialized developmental and epigenetic properties, determine pregnancy outcome independently of their effects over immune cells. Lastly, we study how the uterine adaptation to pregnancy finds parallels in the adaptations of the tumor microenvironment that facilitate tumor escape from immune destruction.
- Mahiddine K, Blaisdell A, Ma S, Créquer-Grandhomme A, Lowell CA, Erlebacher A. Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils. J Clin Invest. 2020 Jan 2;130(1):389-403.
- Nancy P, Siewiera J, Rizzuto G, Tagliani E, Osokine I, Manandhar P, Dolgalev I, Clementi C, Tsirigos A, Erlebacher A. H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition. J Clin Invest. 2018 Jan 2;128(1):233-247.
- Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science. 2012 Jun 8;336(6086):1317-21.
- Tagliani E, Shi C, Nancy P, Tay CS, Pamer EG, Erlebacher A. Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1. J Exp Med. 2011 Aug 29;208(9):1901-16.
- Collins MK, Tay CS, Erlebacher A. Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice. J Clin Invest. 2009 Jul;119(7):2062-73.