# Identity, mechanisms and early life impacts of transporter interfering compounds

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $539,421

## Abstract

PROJECT SUMMARY
Prenatal exposures to environmental chemicals have been shown to cause adverse later life health effects,
often involving disorders of reproductive dysfunction. The overall goal of this research is to understand the
mechanisms governing accumulation of environmental chemicals in the embryo, so that we can predict and
mitigate the negative effects of these exposures. In this proposal, we address two key questions with regard to
xenobiotic accumulation in the embryo, with a specific focus on the role of xenobiotic transporters during
primordial germ cell (PGC) formation. First, we ask how the program of development leads to changes in
xenobiotic transporter expression, and thus generates windows of susceptibility or resistance to xenobiotic
accumulation. Second, we ask how real-world chemical mixtures, containing both substrates and inhibitors of
transporters, impact the efficacy of this conserved, protective system. Aim 1 uses a powerful in vitro molecular
evolution technology to rapidly evolve, validate, and use antibody-like binders called nanobodies to
characterize xenobiotic transporter proteins in human PGC-like cells (PGLCs) and in model organism embryos
(sea urchin and zebrafish). Aim 2 applies biochemical and cellular approaches to determine relevant
environmental ligands of human and model system xenobiotic transporters, and takes advantage of a powerful
molecular structure determination pipeline to dissect the molecular mechanisms of these interactions. Aim 3
uses models and molecular targets from Aims 1 and 2 to test the hypothesis that PGCs are vulnerable to the
interfering effects of environmental chemicals on the transporter defense system, and that disruption of this
system leads to decreased reproductive fitness after xenobiotic challenge. This results will provide new
insights into how environmental and developmental factors act in combination to govern the susceptibility of
the nascent embryonic germ line to teratogens.

## Key facts

- **NIH application ID:** 10424481
- **Project number:** 5R01ES027921-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEOFFREY A CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $539,421
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424481

## Citation

> US National Institutes of Health, RePORTER application 10424481, Identity, mechanisms and early life impacts of transporter interfering compounds (5R01ES027921-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10424481. Licensed CC0.

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