# Diversity Supplement for “Post-translational regulation of LDLR”

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $64,611

## Abstract

ABSTRACT
Elevated plasma LDL cholesterol is the main risk factor in cardiovascular disease (CVD), the
leading cause of death in the United States. Cholesterol levels are regulated by complex feedback
mechanisms that help maintain cellular and plasma cholesterol levels in check. While
transcriptional mechanisms that control cholesterol homeostasis, such as SREBPs and LXRs are
well described, here we describe a novel post-transcriptional mechanism that is involved in
controlling the mRNA stability of Ldlr mRNA. We have identified a family of RNA binding proteins
(RBPs) that target specifically mRNAs and are important in cholesterol homeostasis. We show
that hepatic loss of one or more of these RBPs in the liver results in increased levels of LDLR
mRNA and protein. In Specific Aim 1, we will identify the direct mRNA targets in vivo using CLIP-
Seq and we will perform functional genomics to determine the effect of human variants in the
LDLR 3’UTR. In Specific Aim 2, we will extend our preliminary data showing that loss of one of
our RBPs in the liver profoundly protects from atherosclerosis. Using a ‘humanized’ lipoprotein
mouse atherosclerosis model, we have developed the hypothesis that loss of our RBP in the liver
promotes uptake of LDL particles, thus protecting from atherosclerosis. Further, we hypothesize
that the internalized cholesterol is then preferentially catabolized to bile acids. Thus, our mouse
model will allow us to better understand how the liver channels cholesterol taken up from LDL
particles to ultimately protect from CVD.

## Key facts

- **NIH application ID:** 11098331
- **Project number:** 3R01HL174008-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Elizabeth Joanna Tarling
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $64,611
- **Award type:** 3
- **Project period:** 2024-09-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098331

## Citation

> US National Institutes of Health, RePORTER application 11098331, Diversity Supplement for “Post-translational regulation of LDLR” (3R01HL174008-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11098331. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*