# Investigation of the mitochondrial function in GNAS mutant neoplasms

> **NIH NIH K22** · UNIVERSITY OF CINCINNATI · 2021 · $195,196

## Abstract

Emerging evidences pointing out the requirement of mitochondrial function in the oncogenesis processes, but
how the mitochondrial state is changed in different set of oncogenic mutations is largely obscure. Changes in
mitochondrial metabolism and function are results of mitochondrial dynamics (fission/fusion) and remodeled
mitochondrial proteome. cAMP/PKA pathway has conserved roles in the regulation of mitochondrial function
and dynamics in various physiological processes. The goal of this proposal is to comprehensively analyze the
mitochondrial function and state in a subset of pancreatic cancer those harbor gain-of-function mutations of
GNAS (~60%). In a recent study I discovered mutant GNAS activates cAMP/PKA pathway that leads to
inactivation salt-inducible-kinases (SIKs) and rewiring metabolic processes, a major mechanism required for
tumor growth of these tumors. The global multiplex proteomics data revealed selective remodeling of cellular
proteome by mutant GNAS activation. Specifically there is enrichment proteins of fatty acid oxidation (FAO)
and branched chain amino acid (BCAA) pathways, which are compartmentalized in the mitochondria. Based
on these preliminary data and the pivotal role of cAMP/PKA in controlling mitochondrial dynamics and
metabolism, I hypothesize that mitochondria has profound roles in the oncogenesis process by mutant GNAS.
Building on the solid foundation, this K22 proposal aims to map the GNAS-PKA-SIK mediated changes in
mitochondrial dynamics and proteomic landscape. It will test the hypothesis that the changes in dynamics and
proteome remodeling lead to altered FAO and BCAA pathway function, which are required for growth of GNAS
mutant tumors. Using state-of-art organellar purification, proteomics, metabolic tracing and coupled with
functional assays in pancreatic cancer organoids; I seek to identify the key function of mitochondria in GNAS
mutant cancer. Results from these studies will give unparalleled understanding of oncogenic cAMP signaling in
cancer and may lead to development of new-targeted therapies that can be used in genetically-defined patient
populations.

## Key facts

- **NIH application ID:** 9721914
- **Project number:** 1K22CA237817-01
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Krushna Chandra Patra
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,196
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9721914

## Citation

> US National Institutes of Health, RePORTER application 9721914, Investigation of the mitochondrial function in GNAS mutant neoplasms (1K22CA237817-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9721914. Licensed CC0.

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