Doctoral Dissertation Research: Evolutionary Perspectives on Microchimerism

University Of Washington, Seattle WA

Investigators

Abstract

Beyond conventional genetic inheritance, mothers can impact their offspring's biology through the transfer of immune factors, epigenetic markers, and beneficial microbes. Another lesser-known, non-conventional mode of inheritance is called microchimerism, whereby cells travel between mother and baby during pregnancy, and some colonize and persist for decades after birth. This doctoral dissertation project leverages data from a multigenerational, longitudinal health and nutrition study to investigate microchimerism as a mediating factor in immune tradeoffs throughout the life course. The research aims to better understand how microchimerism may be associated with fetal growth during pregnancy, infant feeding practices, early childhood infectious disease, and pregnancy outcomes in adults. The publicly available data from this longitudinal study and the newly-generated microchimerism data will provide opportunities for student-driven research for undergraduates, including individuals from underrepresented groups. Microchimerism is thought to influence host immune function by directly contributing stem cells that differentiate and develop into functional immune cells and expressing foreign antigens that trigger host immune responses. Most microchimerism research has focused on relationships with autoimmune disorders, cancer, transplant biology, and adverse pregnancy outcomes, leaving considerable gaps in understanding why some individuals are colonized by microchimeric cells more than others, and how these differences might impact evolutionary fitness. To clarify these issues, population-based data from the Cebu Longitudinal Health and Nutrition Survey spanning three generations of participants will be used to investigate the following specific aims: 1) evaluate whether having been breastfed in infancy predicts microchimerism in adulthood, 2) assess whether microchimerism is associated with lower risk of early life infection, and 3) determine whether adult women with microchimerism from their mothers have lower risk of adverse pregnancy outcomes as they have offspring of their own. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.