John Erickson, MD, PhD

My clinical specialty is neonatology. I was inspired to become a neonatologist by the patients themselves, who are so small and innocent. Sick newborn babies have very complex physiology and require a holistic approach to best care for them. I also found that the current understanding of neonatal biology left many unanswered questions and thus provided opportunities to improve the health and lives of my patients. For this reason, I'm also a research scientist aiming to improve the care and outcomes for the tiniest of patients.

Premature birth and other pregnancy complications remain the leading cause of mortality in children each year. Infections in pregnant mothers and neonates also contribute to this alarming epidemic of neonatal deaths. My laboratory studies the immunological changes during pregnancy that enhance neonatal immune defense against pathogens causing serious life-threatening infections while also promoting tolerance between the maternal immune system and developing baby to prevent pregnancy complications. This is a delicate balance that requires many fine-tuned immune responses.

A lifelong interest in immunology and the potential to use immunological tools to improve the lives of children sparked my desire to become a researcher. My PhD research focused on the modulation of checkpoint inhibitors to improve the function of anti-viral T cells. Now, my research aims to better understand the division of labor between humoral and cellular adaptive immune components for effective host defense. Antibodies are thought to offer limited protection against intracellular pathogens since they cannot efficiently cross the plasma membrane to enter most cells. Given their dependence on vertically transferred maternal immunoglobulin G (IgG) for early life immunity, this may explain the prevalence of intracellular infections in fetuses and newborns. In light of this, we recently demonstrated that pregnancy enables antibody-mediated protection against the prototypical intracellular pathogen Listeria monocytogenes (Lm), a major cause of pregnancy loss and sepsis / meningitis in neonates.

The key molecular change during pregnancy is the deacetylation of sialic acid (Sia) located in the terminal position of sugars attached to Lm-specific IgG. Maternal deacetylated IgG then modulates neonatal B cells via the Sia receptor CD22, which can only bind to the deacetylated version of Sia. This establishes a framework whereby differential acetylation versus deacetylation of sialylated IgG serves as a previously unrecognized molecular "switch" that significantly impacts immunity through CD22. We are actively investigating the factors that lead to the generation of antibodies bearing acetylated sialic acid, the cells and enzymes that remodel sialic acid during pregnancy and the coordinated activity of antibodies, cells and cytokines that mediate host defense against neonatal infection. We're also interested in how the sugar molecules attached to proteins can be modulated to improve pregnancy outcomes. I am currently grateful to be NIH-funded to continue these fascinating research studies.

For prematurity and other pregnancy complications, an ounce of prevention is worth more than a pound of cure. Therefore, further research on these topics holds great potential to improve the health of neonates and older children locally and worldwide.