Projects

Lead and the Developing Immune System Study

Evaluation of a human developmental immunotoxicity assay.

Background

Lead exposure is a long-term burden on communities in the United States, due to environmental pollution, past utilization of lead-based paint in homes, and aging infrastructure, with a disproportionate amount of the burden falling upon communities of low socioeconomic status. Lead is a known toxicant to multiple organ systems, including the nervous system, renal system, and the immune system. Although lead has been of acute interest in developmental neurology, little work has been done to investigate the effects of lead on maternal health outcomes and the developing human immune system

Project

The project work is the first to provide a model system to directly determine whether lead is a developmental immunotoxicant in humans, and it will establish associations between adverse pregnancy outcomes and lead exposure during pregnancy. To date developmental immunotoxicants have been almost exclusively identified through the utilization of murine models, lead notwithstanding.

Published epidemiology studies have suggested that exposure to lead can dysregulate the human immune response to influenza and the MMR vaccine. Taken together, these data demonstrate critical gaps in understanding the effects of lead on maternal and pregnancy outcomes, as well as on human immune development.

This study aims to identify disparate levels of lead exposure within our community, which may illuminate health equity disparities and offer future opportunities to address populations with potential developmental alterations in cord blood derived hepatopoietic stem cell (HSC) to immune cell lineage specification due to lead exposure. We will use a multifaceted cellular, molecular, epidemiological and clinical approaches to:

Identify health equity issues within our community and association of blood lead levels with maternal outcomes and pediatric immune dysregulation.
Determine the effects of environmentally relevant concentrations of lead on lineage specification of immune cell development

Investigators

Joe Zagorski, Norbert Kaminski, and Corewell Health

Timeline

Research study design began in March 2022 and funding is secured. Once fund are released, research will commence for 12-16 months.

Working Group: Identification and Validation of Cell-based Assay

Identification and Validation Cell-based Assays for Developmental Immunotoxicity Testing

Overview

It is increasingly clear that the global rise in inflammatory diseases and immune-mediated disorders can be traced back to early development.

The International Working Group on Alternatives to in vivo Developmental Immunotoxicity (DIT) Testing is working to identify and validate new models to serve as an alternative to traditional animal testing models.