# The Role of Dermal Fibroblasts in Skin Cancer

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Basal cell carcinoma (BCC) is the most commonly occurring cancer in humans, and is particularly prevalent in
the Veteran population. BCC is driven by DNA damage to the interfollicular epidermis, the body’s outermost
protective barrier. Preliminary studies demonstrate that DNA damage activates inflammasome signaling in
dermal fibroblasts, which enhances epithelial cell proliferation and plasticity in wild-type interfollicular
epidermis, characteristics that are associated with tumorigenesis. Strikingly, however, the role of dermal
fibroblasts in cutaneous skin cancer development has not been adequately addressed. Cancer-associated
fibroblasts (CAFs) are predominant in tumor stroma, and have been proposed to drive the progression of many
epithelial cancers, including BCC. However, the direct role of CAFs in cutaneous skin cancer progression is
currently unknown. The primary goal of this CDA-2 research proposal is to test the hypothesis that
inflammasome signaling from dermal CAFs promotes BCC development. This research will be the first to
deeply characterize 1) epidermal and dermal live cell dynamics during BCC formation, 2) the role of CAFs in
BCC development, 3) CAF necessity and sufficiency for skin cancer progression, 4) CAF signaling changes
during skin tumorigenesis, and 5) the impact of specific CAF signaling subpopulations on skin cancer cell
behaviors. Transgenic mouse models, live intravital imaging, patient-derived xenografts, 3D organotypic co-
culture, as well as single cell analyses of primary skin cancer tissue from Veteran patients will be employed to
investigate these research aims. In addition, this work will take place in a highly collaborative, supportive and
rigorous research environment, and will be accompanied by both technical training and formal coursework in
cancer mouse models, ex vivo organoids, CRISPR/Cas9 technology, mass cytometry, and single cell RNA
sequencing. The data generated in the CDA-2 training phase, coupled with the extensive technical expertise
and career development skills that will be attained, will provide a strong foundation for the long-term goals of
securing VA MERIT award funding and establishing a successful independent research program at a VA-
affiliated institution. The broad objective of the proposed research is to significantly improve Veteran healthcare
by informing the development of targeted therapies to effectively treat and prevent cutaneous skin cancer.
Additionally, this research may provide important insights into therapeutic approaches for treating other
epithelial cancers as well as inflammatory skin disorders that are also common among Veterans.

## Key facts

- **NIH application ID:** 10692944
- **Project number:** 7IK2BX005370-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Lindsey Nicole Seldin
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 7
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692944

## Citation

> US National Institutes of Health, RePORTER application 10692944, The Role of Dermal Fibroblasts in Skin Cancer (7IK2BX005370-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692944. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*