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NIH grant 1DP2ES039816-01: Reconstructing the Maternal-Fetal Interface: A Placenta–Brain Axis on a Chip Platform to Transform Models of Prenatal Neurotoxicity
Institute: {'code': 'ES', 'abbreviation': 'NIEHS', 'name': 'National Institute of Environmental Health Sciences', 'admin_org_id': '12500022', 'admin_funding_url': ''}. PI: Melissa McKenzie Campbell. Award: $760000.
Start: 2026-08-26T00:00:00.
Project Summary:
Environmental exposures during pregnancy including pesticides, air pollutants, and common
medications are among the most potent yet least understood drivers of adverse
neurodevelopment. Epidemiological studies consistently link such exposures to disorders such
as autism, ADHD, and schizophrenia, but the mechanistic pathways connecting maternal
environment to fetal brain remain a black box.
We will address this gap by building the first placenta–brain axis-on-a-chip: a physiologically
integrated human co-culture system that couples placental trophoblasts, maternal immune cells,
fetal endothelial cells, and cortical organoids via directional microfluidic flow. This platform
recreates the maternal-fetal-brain interface in vitro, enabling real-time tracking of how
exposures traverse the placental barrier and alter fetal brain development. A defining innovation
is the incorporation of next-generation genetically encoded redox biosensors, which allow
continuous, cell-type–specific monitoring of oxidative state: a near-universal pathway of
vulnerability across diverse toxicants.
We hope to determine how maternal exposures alter placental transport and oxidative state in
fetal brain organoids; dissect how oxidative stress perturbs neurogenesis, neuronal migration,
and circuit assembly; and define predictive “oxidative fingerprints” of vulnerability and resilience
across diverse genetic backgrounds, including induced pluripotent stem cell lines from
individuals with autism spectrum disorder.
Preliminary data demonstrate the feasibility of this approach: we have fabricated perfusable
placental barrier chips, validated biosensor integration, and shown oxidative stress responses to
paraquat and acetaminophen exposures that correlate with mitochondrial dysfunction and
neuronal viability.
By resolving the dynamic interplay between maternal exposures, placental physiology, and fetal
brain development, this project will transform how we model prenatal neurotoxicity. The
knowledge gained will establish mechanistic links between maternal environment and child
brain health, inform biomarker discovery, and create a broadly adaptable platform for studying
maternal–fetal interactions in development and disease.document fetched 2026-09-06 02:47