# Understanding mechanism(s)that regulate liver growth and function

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $18,648

## Abstract

Project Summary
The liver processes a broad range of molecules including nutrients, toxins, and drugs. Routine detoxification
of these compounds in the liver is primarily orchestrated by the nuclear receptor Constitutive Androstance
Receptor (CAR). Interestingly, CAR activation by its ligand TCPOBOP (TC), along with increasing the
metabolic potential of the liver, induces hepatic DNA replication and subsequent liver growth. The
mechanisms that facilitate this CAR-dependent liver growth are not fully understood. Unexpectedly, we
discovered that CAR activation can increase de novo dNTP synthesis by inducing the expression of several
enzymes involved in this process including Ribonucleotide Reductase M2 (RRM2). RRM2 is the catalytic
subunit of Ribonucleotide Reductase, the rate-limiting enzyme responsible for dNTP biosynthesis.
Importantly, we found that induction of RRM2 and subsequent increases in the dNTP concentrations were
completely absent in Car-/- mice. These findings indicate that by increasing dNTP synthesis, CAR activation
may afford a cellular milieu that is amenable for DNA synthesis and proliferation. In this proposal, we will
determine (1) if CAR-mediated dNTP synthesis is necessary and sufficient to promote liver growth, and (2)
if CAR-RRM2 axis promotes polyploidy and regeneration in the liver. Overall, this project will not only
uncover the fundamental role for CAR in regulating cellular dNTP levels but also identify novel
mechanism(s) by which CAR achieves its mitogenic effects.

## Key facts

- **NIH application ID:** 10412480
- **Project number:** 3R01DK113080-05S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Sayeepriyadarshini Anakk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $18,648
- **Award type:** 3
- **Project period:** 2017-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412480

## Citation

> US National Institutes of Health, RePORTER application 10412480, Understanding mechanism(s)that regulate liver growth and function (3R01DK113080-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10412480. Licensed CC0.

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