# Exploring the Role of Drp1 in Colorectal Cancer

> **NIH NIH F31** · UNIVERSITY OF KENTUCKY · 2022 · $35,137

## Abstract

Abstract - Exploring the Role of Drp1 in Colorectal Cancer.
 Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Approximately
150,000 new cases and 50,000 deaths are predicted for the year 2020. Emerging research suggests that the
dysregulation of mitochondrial fitness due to an imbalance in mitochondrial dynamics can lead to metabolic
reprogramming in various cancer types. A number of epidemiological studies indicate that obesity is as a major
risk factor for several types of cancer including colorectal cancer. Our group and others have shown that
increased uptake of fatty acids promotes the development and progression of difference cancers by altering
metabolic pathways to favor mitochondrial fatty acid oxidation. However, the molecular mechanisms by which
fatty acid consumption influences mitochondrial fitness to promote tumor cell survival and progression is poorly
understood. In this proposed study, I plan to investigate the signaling crosstalk between mitochondrial dynamics
and fatty acid metabolism in colorectal cancer. In my preliminary experiments, I discovered that fatty acid uptake
promotes mitochondrial fragmentation by activating Drp1, a small GTPase required for mitochondrial fission, by
increasing the phosphorylation at the S616 site and its interaction with mitochondria. Importantly, silencing Drp1
inhibits cancer stem cell functions by attenuating Wnt signaling in colon cancer cells. The central hypothesis is
that Drp1-dependent mitochondrial fission is required for fatty acids to promote tumor progression in colon
cancer. Specifically, I will determine how fatty acid uptake alters Drp1 activity and how mitochondrial dynamics
augments cancer stem cell functions to drive tumorigenesis in vivo. The following specific aims are proposed:
1) to delineate the molecular mechanism by which fatty acid uptake enhances Drp1 activity; 2) to determine the
functional importance of Drp1 in promoting CSC functions in colorectal cancer; and 3) to define the role of Drp1
in regulating tumorigenesis using in vivo colon cancer models. Results from this study will provide novel insights
into the role of mitochondrial dynamics in connecting cellular metabolic pathways with cancer stem cell signaling.
Dr. Gao has extensive experience in studying the regulation of signaling pathways and mitochondrial metabolism
in colorectal cancer. I will also benefit from additional expertise provided by my committee members and state-
of-the-art facilities of the Markey Cancer Center at the University of Kentucky. A comprehensive training plan
has been developed to fit my research background and career goals. Based on my strong preliminary data, with
my mentor’s knowledge and training, and the excellent research environment at the Department of Molecular
and Cellular Biochemistry and the Markey Cancer Center I am confident that this project will be successful.
Ultimately, this study will help develop personalized treatment op...

## Key facts

- **NIH application ID:** 10373964
- **Project number:** 5F31CA260840-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Sumati Raj Hasani
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,137
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373964

## Citation

> US National Institutes of Health, RePORTER application 10373964, Exploring the Role of Drp1 in Colorectal Cancer (5F31CA260840-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10373964. Licensed CC0.

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