# Dissecting Fatty Acid Metabolism in Clear Cell Renal Cell Carcinoma (ccRCC)

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $34,757

## Abstract

PROJECT SUMMARY/ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the most devastating form of human kidney cancer and is marked by
significant accumulation of lipids and dysregulated glutathione metabolism. However, the role of lipids in ccRCC
pathogenesis is poorly understood despite evidence that aspects of lipid metabolism correlate with worse patient
survival. Although glutathione metabolomics signatures can be strong predictors of ccRCC metastasis and
progression, we do not have a clear understanding of glutathione and redox biology in ccRCC. This proposal
aims to dissect the molecular underpinnings of ccRCC lipid metabolism, specifically fatty acid biosynthesis, and
the interplay of lipid metabolism with glutathione metabolism in ccRCC. Glutathione metabolism and lipid
metabolism are seemingly linked through the reducing equivalent NADPH. NADPH is required to regenerate
reduced glutathione (GSH) but it also required to synthesize fatty acids. We will utilize stable isotope tracing in
human patients and patient derived xenograft (PDX) ccRCC mouse models to accomplish this goal. The Specific
Aims of this proposal intend to (1) compare the contribution of fatty acid biosynthesis and extracellular fatty acid
uptake to ccRCC lipid accumulation, (2) test how fatty acid metabolism contributes to redox and glutathione
homeostasis, and (3) understand ccRCC lipid metabolism in living human patients. We will use stable isotope
infusions of 13C-labeled metabolites to identify and pinpoint pathways of lipid metabolism that are highly active
in human ccRCC patients. We will then use PDX models that faithfully recapitulate clinical ccRCC to
systematically dissect the observations we see in humans. Altogether, these Aims will generate new data and
insights into an underexplored area of ccRCC biology with unprecedented relevance to human disease. The
findings of this proposal could point to a mode of metabolic reprogramming applicable to multiple cancer types
and have strong implications for therapeutic intervention for ccRCC patients.

## Key facts

- **NIH application ID:** 10101636
- **Project number:** 5F31CA239330-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Divya Bezwada
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,757
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101636

## Citation

> US National Institutes of Health, RePORTER application 10101636, Dissecting Fatty Acid Metabolism in Clear Cell Renal Cell Carcinoma (ccRCC) (5F31CA239330-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10101636. Licensed CC0.

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