# A human neurodevelopmental model of Fetal Alcohol Spectrum Disorders

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $137,249

## Abstract

SUMMARY
Fetal Alcohol Spectrum Disorder (FASD) covers the broad variety of adverse developmental outcomes found in
children as a consequence of prenatal alcohol exposure. The effects observed in FASD range from
neurobehavioral abnormalities to embryonic lethality, depending on the developmental stage and severity of the
exposure. However, the limited availability of live human brain cells for research has impaired progress toward
understanding mechanisms behind FASD. Human pluripotent stem cells (hPSC) are poised to revolutionize our
ability to make mechanistic inferences, bridging the gap between traditional model systems and human biology.
Differentiation of hPSC allows for the study of brain development in-a-dish, providing a platform with greater
accessibility to alcohol exposure experimental manipulation. We hypothesize that alcohol exposure at early
stages of human development leads to epigenetic modifications, affecting gene expression and causing
physiological changes at the cellular and functional levels.
Our aims are: (i) Determine the transcriptional and epigenetic landscape of alcohol exposure. We will
generate hPSC-derived organoids, which recapitulate the mid-fetal human cortical development, and expose
them to alcohol at different maturation time points. We will perform unbiased gene expression by RNAseq,
followed by DNA methylation profiling. The correlation of this data will reveal the signature of genes that are
more dramatically affected by alcohol during neurodevelopment. (ii) Measure the physiological
consequences. The anatomical analysis of these human brain organoids will provide information about the
consequences of alcohol exposure for cortical cytoarchitecture and layer identity. Cell death and proliferation will
be evaluated. We will perform a battery of morphometric and physiological tests to determine the impact of
alcohol in hPSC-derived progenitors, neurons, and astrocytes. Real-time synaptogenesis assay will be
performed to determine when synapses become defective under alcohol exposure. (iii) Evaluate the neural
network alteration and functional rescue. We will investigate neuronal connectivity by evaluating network
synchronization using multi-electrode arrays. This technology will allow us to define the subpopulations content
of neural cultures affected by alcohol exposure Finally, we will manipulate potential genes and molecular
pathways to rescue potentially altered phenotypes. We will perform basic gain and loss of function to rescue the
FASD neuronal connectivity defects. We strive to offer a multidisciplinary approach which has the potential to
identify biomarkers for FASD could impact the future treatment options for children exposed to alcohol prenatally.

## Key facts

- **NIH application ID:** 9985674
- **Project number:** 5K01AA026911-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Cleber A Trujillo
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $137,249
- **Award type:** 5
- **Project period:** 2018-10-31 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985674

## Citation

> US National Institutes of Health, RePORTER application 9985674, A human neurodevelopmental model of Fetal Alcohol Spectrum Disorders (5K01AA026911-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985674. Licensed CC0.

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