# MicroRNAs as regulators of drug metabolism and transport in pregnant and lactating women

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $168,814

## Abstract

It is becoming increasingly evident that epigenetic mechanisms such as micro (mi) RNAs modify the production
of drug receptors, metabolizing enzymes and drug efflux transporters thus affecting therapeutic dose, resistance
and toxicity. Altered expression and bioavailability of drug metabolizing enzymes and transporters (DMETs) has
been observed in pregnant and lactating women with the potential to affect not only mothers but also child health
and development. Mechanistic understanding of this site of pregnancy physiology and how miRNAs targeting
DMETs are regulated in these two unique life settings is largely unexplored. MicroRNAs are small, non-coding
RNAs that negatively regulate gene expression at the post-transcriptional level by inducing translational inhibition
or mRNA degradation. They are encoded by their own genes or within introns and mature through a multistage
process, both of which controlled by a variety of exposures not yet deciphered in pregnant women. Under a
recently NICHD-awarded 5 R01HD099091-02 we are utilizing large cohorts of Ugandan, Zimbabwean and US
women to make inroads in identifying hormonally and microbiome-regulated miRNAs that convey resistance or
susceptibility to infection in reproductive age women – an area of research unexplored to date. In just one year
of funding we published results in two original articles and a presentation at the international Conference on
Retroviruses and Opportunistic Infections (CROI 2020). The extant metadata catalog includes rich demographic
and behavioral factors, infection status, systemic and mucosal levels of innate immunity biomarkers predictive
of sexually transmitted infections, dysbiosis and HIV, and systemic levels of endogenous estradiol, progesterone
and sex-hormone binding globulin. The current R01 is focused on hormonal contraceptive use and therefore has
excluded pregnant and lactating women from the global miRNA transcriptome analysis but we have all metadata
available for these women and their longitudinal samples. This response to NICHD NOT-HD-20-003 proposes
to leverage existing biospecimens, data and technological resources accumulated during the parent R01 and
expand testing to include existing biospecimens from pregnant and lactating women toward the following aims:
1) determine effect of pregnancy and breastfeeding on levels of validated miRNAs regulating DMETs; 2) explore
reproductive hormones- and microbiome-driven enrichment for miRNAs targeting known placental drug
transporters; 3) identify miRNAs differentially expressed during pregnancy or breastfeeding known to regulate
exposure to antiviral and anti-inflammatory drugs, with emphasis on drugs with limited pharmacokinetics studies
in these conditions exemplified by experimental therapeutics for COVID-19. The proposed research will generate
high-dimension data to become available through the NICHD DASH. It will open the door to novel in silico
predictive models of drug safety and availability in pregnant a...

## Key facts

- **NIH application ID:** 10177227
- **Project number:** 3R01HD099091-02S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** RAINA N. FICHOROVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,814
- **Award type:** 3
- **Project period:** 2019-05-13 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177227

## Citation

> US National Institutes of Health, RePORTER application 10177227, MicroRNAs as regulators of drug metabolism and transport in pregnant and lactating women (3R01HD099091-02S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10177227. Licensed CC0.

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