# Myc-induced expression of glutamine synthetase

> **NIH NIH K00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $102,501

## Abstract

Project Summary
This is a F99/K00 application which will encompass my predoctoral and postdoctoral training. I have described
my research experience which pertains to my completed dissertation work in Aim 1. My training plan for
dissertation work to be completed and skills to be gained are highlighted in Aim 2. Finally, Aim 3 describes my
future training plans for the postdoctoral fellowship phase. My topic of research during my predoctoral training
(F99) period is focused on understanding the regulation of glutamine metabolism by the oncogene Myc. Myc
oncoprotein is known to drive reprogramming of energy metabolism to meet the needs of energy consumption,
macromolecule biosynthesis, and waste disposal in cancer cells. Cancers with elevated level of Myc exhibit an
increased dependency on glutamine, which has been attributed to glutaminase (GLS), the enzyme catalyzing
the deamination of glutamine into glutamate to fuel the tricarboxylic acid (TCA) cycle. Intriguingly, my sponsor
Dr. Wei-Xing Zong’s laboratory recently found that Myc can induce the expression of glutamine synthetase
(GS), the enzyme that catalyzes the reverse reaction of GLS, to promote the de novo synthesis of glutamine
from glutamate and ammonia. My preliminary data demonstrate that ectopic GS expression leads to elevated
glutamine that is used for nucleotide synthesis, uptake of essential amino acids, increased cell
growth/proliferation/survival, and tumorigenesis. These data prompt the formation of the hypothesis that GS is
a critical mediator of Myc-driven tumorigenesis by generating glutamine to meet the increased demand of
glutamine in cancer cells. Three specific aims are proposed to test this hypothesis: 1) Determine the metabolic
role of GS in the context of Myc activation; 2) Study the biological consequences of GS under Myc induction; 3)
Explore the role of GS in vivo. Accomplishment of this project will unravel a novel mechanism through which
Myc promotes reprogramming of cancer cell metabolism, and will help to establish GS as a therapeutic target.
This study will also offer a unique opportunity for me to receive top-notch training in both oncogenic signaling
and in cancer cell metabolism, which will largely help me to transition to the postdoctoral phase (K00) which is
an instrumental step to achieve my career goal to become an independent cancer biologist.

## Key facts

- **NIH application ID:** 10002027
- **Project number:** 5K00CA212445-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Alex Bott
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $102,501
- **Award type:** 5
- **Project period:** 2016-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002027

## Citation

> US National Institutes of Health, RePORTER application 10002027, Myc-induced expression of glutamine synthetase (5K00CA212445-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10002027. Licensed CC0.

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