# Diversity Supplement to Role of Wnt/beta-catenin In Liver Regeneration

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $60,839

## Abstract

End stage liver disease is a major cause of morbidity and mortality worldwide and in the USA, where it is the 12th
leading cause of death. Hence, innovative research to promote liver repair is critical. Critically, we and others
identified the Wnt/b-catenin signaling pathway as key for liver regeneration and repair. We also showed this
pathway’s key roles in hepatic metabolic zonation (MZ) and liver regeneration (LR) after partial hepatectomy
(PH). The impetus behind requesting a diversity supplement to our current R01 is two-fold. An exceptionally
talented and driven graduate student from an underrepresented minority with an interest in Wnt signaling and
organ regeneration is highly interested in pursuing her graduate training in our lab. And, her work and interests
are a logical extension of the existing R01’s specific aims. Thus, broadening the scope of the current studies
through innovating imaging and spatial transcriptomics with focus on Wnt-Frizzled signaling would add further
impact and innovation and promote diversity in the lab. Specifically, we are extending aims 2 and 3 of the original
grant by proposing two aims. Specific Aim 1 for the Diversity Supplement will create a temporospatial atlas
of Fzd receptor mRNA expression, first in the normal liver as a baseline, and then in liver undergoing
regeneration after PH. We will employ multiplex RNAscope to directly and quantitatively visualize zone-specific
expression of all 10 Fzd receptors. These studies will shed light on aspects of basic liver zonation, which is
crucial for creating a foundation to further investigate liver biology, both structurally and functionally. It would also
allow for a differential comparison of zonation and Fzd expression between normal and regenerating liver post-
PH, which will help reveal molecular mechanisms responsible for LR as well as re-establishing zones after PH.
This aim is an extension of the current Aim 2 of the existing proposal which focuses on examining an in-depth
role of Fzd7 in zonation and after PH. Based on analysis performed on hepatocyte-specific Fzd7-knockout mice,
we found no defect in MZ or LR after PH. This led us to propose spatial transcriptomics through RNA scope for
all Fzds at baseline in liver and then after PH. Specific Aim 2 of the supplement will elucidate the early
changes in the expression of Wnt2 and Wnt9b during the process of LR. Using RNAscope, we will study
changes in temporospatial patterns of Wnt2 and Wnt9b expression at early time points after PH in normal mice
and in specific KO models, including endothelial cell-specific Wnt2 and Wnt9b single and double KOs. This is an
extension of Aim 3 which examines hypoxia and shear stress as upstream effectors of Wnt signaling in liver.
However, visualizing cell-specific changes in gene expression of Wnt2/9b by RNAscope as a function of time,
will provide us a more solid rationale for studying dynamics of Wnt2/9b control of LR. In conclusion, by creating
an temporospatial at...

## Key facts

- **NIH application ID:** 10153257
- **Project number:** 3R01DK062277-17S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Satdarshan Singh Monga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $60,839
- **Award type:** 3
- **Project period:** 2004-01-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153257

## Citation

> US National Institutes of Health, RePORTER application 10153257, Diversity Supplement to Role of Wnt/beta-catenin In Liver Regeneration (3R01DK062277-17S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10153257. Licensed CC0.

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