# Examining the impact of the obesity-inflammation axis on cancer by genomic and transcriptomic profiling

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $72,563

## Abstract

Project Abstract:
Obesity is associated with over 630,000 (40%) of all new cases of malignant neoplasms diagnosed
annually in the United States1, and a high body mass index (BMI) increases the risk of over seventeen
types of solid tumors2. Mounting evidence suggests that in addition to promoting cell proliferation,
obesity may also drive the development of cancer by creating a state of chronic inflammation. Moreover,
adiposity and high fat diet (HFD) has been shown to promote reactive oxidative stress (ROS) and
impede normal immune function. Recent pan-cancer analyses have identified somatic mutation
signatures associated with specific etiologies that promote cancer, such as cigarette smoke, UV
radiation, defects in DNA repair, aging and possibly, inflammation. The genomic and functional impact of
obesity, and its connection to inflammation, have not been well-elucidated in humans due to complex
genetic and environmental heterogeneity. Previous work by our lab and others has identified carcinogen
and ROS-related mutation signatures in mouse models of human cancers. In addition, using an
interspecific backcross mouse model of skin cancer, we identified quantitative-trait loci (QTL) linked to
high BMI, increased papilloma burden and progression to carcinomas. A significant female-specific QTL
was centered on the leptin receptor gene (LEPR), whose expression is strongly correlated with genes
enriched for cytokine signaling and immune response. Here, using established models of genetic and
dietary obesity in mice, I will investigate possible mechanisms by which obesity or HFD can promote
cancer. First, I will test the hypothesis that obesity mediates a chronic inflammatory response that
promotes cancer by creating patterns of somatic mutation signatures consistent with excess ROS
production, advanced cellular aging, or impaired DNA repair by determining with whole-genome
sequencing if there is evidence of an obesity-associated genomic tumor mutation signature. Next I will
test the hypothesis that obesity promotes upregulation of adipokine signaling pathways in tumors and
stromal cells and induces transcriptomic signatures of inflammation in tumor-infiltrating immune cells.
Finally, I will evaluate if dietary obesity affects the proliferation or development of cancer stem cells by
performing lineage tracing using an inducible-Cre reporter mouse expressing LGR6, a stem cell marker
of carcinomas in epithelial tissues. Together, using state-of-the-art multi-omic, computational and
molecular tools, these aims will evaluate the role of the obesity-inflammation axis in promoting cancer
and identify candidate genetic, functional and developmental targets for downstream mechanistic
studies and therapeutic avenues.

## Key facts

- **NIH application ID:** 9968193
- **Project number:** 5F32CA232635-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yun Rose Li
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,563
- **Award type:** 5
- **Project period:** 2018-07-18 → 2021-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968193

## Citation

> US National Institutes of Health, RePORTER application 9968193, Examining the impact of the obesity-inflammation axis on cancer by genomic and transcriptomic profiling (5F32CA232635-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9968193. Licensed CC0.

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