# Role of Prematurity and Sterol Metabolism in Parenteral Nutrition-Associated Liver Disease

> **NIH NIH K23** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $177,716

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this proposal is to provide a pathway to independence as a clinical-translational investigator in the
nutrition of premature and critically ill infants. Total parenteral nutrition (TPN) is one of the most common
therapies provided in the neonatal intensive care unit (NICU). However, the safety of TPN is significantly
limited by the risk for parenteral nutrition-associated liver disease (PNALD). Plant sterols in the soy-based lipid
component of TPN are believed to be a contributing factor to liver injury. My prior studies showed that plant
sterols are markedly elevated in infants with PNALD and that age impacts sterol metabolism and expression of
important hepatic sterol-regulating genes. Two critical gaps in knowledge exist in our understanding of PNALD:
1) the ability of infants to manage exogenous plant sterols during prolonged soy lipid exposure and 2) the
mechanism that underlies the vulnerability of neonates to PNALD. My overarching career goal is to close the
knowledge gap by becoming an expert in sterol metabolism and PNALD in order to develop and apply novel
interventions to improve the safety of TPN in infants. My career development plan logically extends my prior
training in neonatology and clinical research. I will attain knowledge and training in translational research,
sterol-regulating pathways, iPSC-derived hepatocytes, and liver development. Experienced mentors and a
scientific advisory committee at the Medical College of Wisconsin, University of Cincinnati, and the NIH with
expertise in multi-center translational research, sterol metabolism, stem cell technologies, and liver
development will guide me. I hypothesize that plant sterol concentrations associated with increased risk
for PNALD are influenced by gestational age and failure to express key sterol-regulating genes. I will
test this hypothesis through two specific aims. Aim 1 seeks to determine the kinetics of serial plant sterol
accumulation and their association with cholestasis in infants receiving prolonged soy lipids. This will be done
using a prospective, multicenter clinical study to measure serial plant sterol and cholesterol levels in the
blood of infants during soy lipid therapy of at least 2 weeks. Aim 2 seeks to identify gene expression and lipid
accumulation in patient-derived hepatocytes exposed to plant sterols at different developmental stages. This
will be assessed using immature and mature hepatocytes derived from the iPSC of matched study participants
with and without PNALD. Results and expertise acquired during this award will position me to establish an
independent, clinical-translational research program to ultimately improve the safety of nutrition in critically ill
neonates.

## Key facts

- **NIH application ID:** 10129951
- **Project number:** 5K23DK109071-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Tuyet-Hang Nghiem-Rao
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $177,716
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129951

## Citation

> US National Institutes of Health, RePORTER application 10129951, Role of Prematurity and Sterol Metabolism in Parenteral Nutrition-Associated Liver Disease (5K23DK109071-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129951. Licensed CC0.

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