# The role of PLAG1 in Wilms tumor formation

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $154,485

## Abstract

PROJECT SUMMARY/ABSTRACT
 I am a pediatric oncologist and physician-scientist at the University of Texas Southwestern Medical
Center. My long-term goal is to become an independent investigator studying the genetic drivers of Wilms
tumor and ways to therapeutically target them. Wilms tumor is the most common pediatric kidney cancer.
Although most children are cured, those with high-risk disease continue to have poor outcomes. These tumors
are thought to arise from nephron progenitor cells that proliferate instead of differentiating. However, no
alternative, targeted therapies have proven effective in Wilms tumor.
 I previously discovered that some Wilms tumors are driven by mutations that impair production of
microRNAs, an important class of molecules involved in gene regulation. Further, Wilms tumors with and
without these mutations overexpress the oncogene PLAG1. Thus, the central hypothesis to be tested here is
that PLAG1 overexpression in the developing kidney impairs differentiation and drives proliferation, leading to
Wilms tumor formation. I will test this hypothesis with the following Specific Aims:
Aim 1. To test whether miRNA repression of Plag1 is required for nephron differentiation.
Aim 2. To determine whether PLAG1 expression is sufficient for tumorigenesis.
Aim 3. To identify the downstream effectors of PLAG1 in nephron progenitor cells (NPCs).
To carry out these studies, I have developed an integrated career development plan which will allow me to
develop skills with cutting-edge in vitro and in vivo techniques, especially ex vivo culture of NPCs. As part of
this plan I have assembled an advisory committee with extensive mentoring experience in cancer biology who
will oversee my scientific and career development: Dr. James Amatruda and Dr. Joshua Mendell (co-mentors);
Dr. Thomas Carroll; Dr. James Brugarolas; and Dr. Sean Morrison. The studies described herein will allow me
to elucidate how PLAG1 contributes to Wilms tumor formation. I anticipate that they will propel me towards a
career as an independent investigator studying PLAG1 and other genetic factors contributing to Wilms tumors
and other childhood cancers.

## Key facts

- **NIH application ID:** 10197813
- **Project number:** 5K08CA207849-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Kenneth Sung-Man Chen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $154,485
- **Award type:** 5
- **Project period:** 2017-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197813

## Citation

> US National Institutes of Health, RePORTER application 10197813, The role of PLAG1 in Wilms tumor formation (5K08CA207849-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197813. Licensed CC0.

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