# Elucidating AHR signaling interplay in orofacial clefting and endocrine disruption using microplate microfluidics

> **NIH NIH R00** · MICHIGAN STATE UNIVERSITY · 2020 · $248,998

## Abstract

There is currently a great opportunity in the field of toxicology to identify particularly hazardous chemicals,
implement solutions to reduce exposures to prevent human birth defects and other harms. The number of new
chemicals produced annually has long outpaced the rate of toxicity testing, such that there is backlog of ~80,000
chemicals that have not undergone testing. New approaches to tackle this problem in the field of toxicology are
ongoing, and there is a need to integrate advances in engineering to address shortcomings in modern toxicology
and enable an improved fundamental understanding of toxicity. Hormone signaling and other cellular “crosstalk”
are particularly sensitive to chemical disruption but studying these interactions in vitro (in a dish, rather than an
animal) has been hindered by the increased complexity associated with adding multiple pieces of biology
together in meaningful way. Through world-class interdisciplinary training in engineering multicellular models
(postdoc), and molecular and environmental toxicology (PhD), I have positioned myself to tackle this problem as
a 21st Century Toxicologist. In this proposal, I will develop an important independent research track integrating
the needs and solutions of engineering and toxicology. My career goal is to lead an interdisciplinary research
group to identify unknown problem chemicals and study their mechanisms of toxicity, and prevent birth defects
and other harms To achieve this goal, I worked with an experienced and interdisciplinary mentoring committee
to identify weaknesses in my training and plan career development and training opportunities to address them
and further distinguish me from my mentors. A detailed training checklist was constructed to facilitate completion
of the Training and Research Plan, develop new collaborations at other institutions and to help achieve
independence. Predicting the risks posed by chemical exposure is challenging in part because chemicals can
target distinct signaling pathways or parts thereof at once and interact to block or activate important biology. In
this proposal, I will test the hypothesis that multi-cellular “tissue-on-a-chip” models will allow us to identify new
chemicals whose toxicity is yet unknown... Chemicals are not designed like drugs are and can interact in the
body in unpredictable ways. I have worked to invent two in vitro models that integrate advances in engineering
and microfluidics to address shortcomings in 21st century toxicity testing. We have tested the ability of one
platform to model teratogenicity in cleft lip and palate (CL/P) and will continue to develop that line of research in
this proposal. The other platform is built for robotic chemical testing, but reduces false-positive and false-negative
tests by adding the function of the liver. Overall, this career development plan will allow me to establish myself
as an expert and leader in the field of 21st Century Toxicology, emphasizing the toxicity of i...

## Key facts

- **NIH application ID:** 10237474
- **Project number:** 4R00ES028744-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Brian P. Johnson
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,998
- **Award type:** 4N
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237474

## Citation

> US National Institutes of Health, RePORTER application 10237474, Elucidating AHR signaling interplay in orofacial clefting and endocrine disruption using microplate microfluidics (4R00ES028744-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10237474. Licensed CC0.

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