Investigating How Immune Responses Are Regulated

Projects are broadly focused on overlapping scientific platforms investigating how immune responses are regulated, with particular focus on the maternal responses to babies, maternal response to microbes, babies response to mothers, and babies response to microbes; with the generous support by the NIH through multiple investigator initiated R01 awards, the Burroughs Wellcome Fund Infectious Disease Pathogenesis award, and the March of Dimes Ohio Collaborative on Prematurity Research.

How Mothers Remember Their Babies?

One striking epidemiological features of prematurity and other human pregnancy complications is the protective benefits of prior health pregnancy against developing complications in future pregnancy. We actively investigate the changes left in mothers after pregnancy to determine how protection against complications in future pregnancy is mediated. This includes the persistence of maternal memory immune cells with fetal specificity, and microchimeric cells (cells of fetal origin that reside in mothers) as a potential source of ongoing fetal antigen “reminders”.

Vertically Transferred Protection from Mothers to Babies

Our laboratory pioneered studies demonstrating hypo-responsiveness of neonatal immune cells reflects active suppression in the neonatal window, instead of cell-intrinsic immaturity. Active suppression at the time of birth averts pathological inflammation in mucosal barrier tissues in response to primary commensal colonization. This understanding led us to projects focused on vaccinating mothers and reproductive age women to boost immunity in the perinatal window, instead of developing neonatal vaccines with increased immunogenicity.

Immunity to Commensal / Pathobiont Microbes

Our mucosal barrier tissues are colonized with literally trillions of microbes. Colonization in this context primes immunological awareness without pathological inflammation. We investigate this more ancient form of tolerance to antigenically foreign cells to cross foster new ways to think about reproductive tolerance, and to shed new light on the immune pathogenesis of autoimmune-autoinflammatory disorders including inflammatory bowel disease.

Transplantation Tolerance

Transplantation is the most definitive therapy for millions of individuals with end organ failure. We investigate how tolerance to organ allografts to cross foster new ways to think about reproductive tolerance, and to shed new light on how to protect transplantation recipients against infection and allograft rejection.

Human Pregnancy

We investigate how pregnancy impacts the responsiveness of women to common public health interventions including vaccines and mouthwash, and in turn how these interventions impact upon pregnancy and neonatal outcomes.