# Mechanism of regulation of Down Regulated Adenoma (DRA) in obesity associated colitis induced colon cancer

> **NIH NIH P20** · MARSHALL UNIVERSITY · 2020 · $198,002

## Abstract

Obesity has been associated with increased risk and early onset of colon cancer. About 40% of obesityrelated 
cancer incidences were recorded in the United States. More specifically in West Virginia, 49% of 
obesity-associated incidences of colon cancer and 18% of associated mortality rate have been 
documented. Similarly, inflammatory bowel disease (IBD) (ulcerative colitis (UC) and Crohn’s disease 
(CD)) is known to be an important risk factor for the development of colon cancer, namely colitis-associated 
colon cancer (CAC). CAC is preceded by clinically detectable IBD. UC increases CAC risk up to 18-20% 
while CD contributes up to 8% after 30 years of active disease. It has been demonstrated in the colon in an 
in vivo genetic obesity model (Zucker rats) and in in vitro in Adipocyte Derived Secretome (ADS) model of 
obesity that chloride absorption is mediated by the Cl-/HCO3- exchanger DRA was significantly decreased. 
Similarly, in a rat model of colitis and in CAC, DRA was downregulated. This indicates that alteration of 
regulation of chloride absorption is a common factor in both obesity and colon cancer models. However, if 
downregulation of DRA mediated chloride absorption might specifically be responsible for the onset and 
progression of obesity or colitis-associated colon cancer is not known. Therefore, we hypothesized that the 
downregulation of Cl-/HCO3- exchanger DRA in colon in obesity or in colitis increases the risk of colon 
cancer onset and progression. The overall aim of the proposed project is to determine the mechanism of 
regulation of Cl-/HCO3- exchange in the colon in obesity and colitis mediated colon cancer. To decipher 
this, a Zucker rat genetic model of obesity and colitis-associated colon cancer will be used. These animal 
models will be used to induce colon cancer with DSS and Azoxymethane to determine the functional and 
molecular mechanism of the regulation of DRA in obesity and colitis-associated colon cancer. Following will 
be the specific aims of this proposal. Specific Aim 1: To Determine the mechanism of regulation of DRA in 
the colon during obesity. Specific Aim 2: To Define the regulation of DRA in obesity mediated colon cancer. 
Specific Aim 3: To Determine the mechanism of regulation of DRA in colitis during obesity. Specific Aim 4: 
To Delineate the mechanism of regulation of DRA in colitis-associated colon cancer during obesity. This 
proposal will indeed address the lacunae in the understanding of downregulation of DRA, which may play a 
critical role in the pathogenesis of obesity, obesity-associated colon cancer, colitis and CAC. Successful 
completion of these studies as a COBRE ACCORD investigator will provide the necessary training and 
generation of preliminary data to compete for an NIH R01 and become an independent investigator.

## Key facts

- **NIH application ID:** 10452801
- **Project number:** 5P20GM121299-03
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Balasubramanian Palaniappan
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,002
- **Award type:** 5
- **Project period:** 2020-12-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452801

## Citation

> US National Institutes of Health, RePORTER application 10452801, Mechanism of regulation of Down Regulated Adenoma (DRA) in obesity associated colitis induced colon cancer (5P20GM121299-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10452801. Licensed CC0.

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