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Michigan Postdoctoral Pioneer Program, 2020

Collaborative PIs

Mentor

Lonnie Shea, Ph.D.

William and Valerie Hall Chair, Biomedical Engineering
Steven A. Goldstein Collegiate Professor, Biomedical Engineering
Website:
https://shearesearch.engin.umich.edu/
Email:
ldshea@umich.edu

Co - Mentor

Ariella Shikanov, Ph.D.

Associate Professor
Biomedical Engineering
Website:
https://shikanov.engin.umich.edu/
Email:
shikanov@umich.edu

Abstract:

Title:

Monitoring of Fetal Antigen-Presenting and Regulatory T Cells in Pregnancy

Maternal-fetal interactions underlie common diseases of pregnancy, including failed embryo implantation, pre-eclampsia and stillbirth. During early pregnancy the uterine mucosa transforms into the decidua, where the fetal placenta implants and placental trophoblast cells intermingle and communicate with maternal cells. During this process mothers are seeded with genetically foreign fetal cells which persist long after parturition.1,2 For successful pregnancy and parturition, immune effector cells with fetal specificity must be selectively silenced, requiring that the population of immune-suppressive maternal regulatory T cells (Treg cells) expand.3 Additionally, innate cells have been identified with distinctive immunomodulatory and chemokine profiles. Using our minimally-invasive biomaterials-based technology for monitoring immune responses during cancer and autoimmune disease progression, we will investigate the dynamic immune cell populations and phenotypes throughout pregnancy in mice. We anticipate identifying the time course at which the immune signature progresses and changes throughout pregnancy. Furthermore, we will analyze Treg populations from conception, parturition and through a second pregnancy, as fetal-specific Treg cells are proposed to remain elevated and acutely re-accumulate in subsequent pregnancies.1 Modulating the abundance of Tregs will be investigated for the impact on both primary and secondary pregnancy outcomes. This persistence of fetal antigen-expressing cells may represent altruism of first children to promote tolerance in mothers to genetically-similar future siblings.5 The development of an implant to monitor the progression of pregnancy, predict and possibly prevent pathological outcomes could transform current clinical approaches in obstetrics.

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