# In vivo characterization of keratinocytes in the melanoma microenvironment

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $50,175

## Abstract

PROJECT SUMMARY
Melanoma is the most lethal of skin cancers, with progression to local invasion and metastasis leading to poor
patient outcomes, highlighting the need for better understanding of melanoma progression. During melanoma
progression, tumorigenic cells must overcome growth restraints imposed by the microenvironmental
keratinocytes. Although much is known of keratinocyte regulatory controls on normal melanocytes, less is known
about their interactions in melanoma. Our preliminary data suggests that melanoma induces an epithelial-to-
mesenchymal transition (EMT) program in adjacent keratinocytes In Aim 1, I will investigate the role of
keratinocyte EMT on melanoma initiation. For this study, I will use the zebrafish as an animal model to study
in vivo interactions between keratinocytes and melanoma cells. I will induce spontaneous melanoma formation
in transgenic zebrafish lines with GFP labeled keratinocytes and use imaging to confirm morphological changes
indicative of EMT in tumor-associated keratinocytes (TAKs). Then, I will assess them for EMT transcription factor
and adhesion protein changes. We hypothesize that melanoma-induction of keratinocyte EMT will result in loss
of keratinocyte regulation on melanoma proliferation. We will test this hypothesis by knocking out EMT
transcription factors in keratinocytes and assess effects on melanoma initiation and proliferation in the zebrafish
model. In addition, our preliminary data has also highlighted an upregulation of paracrine signals from TAKs
involved in melanoma migration and invasion. In Aim 2, I will determine how keratinocyte-derived secreted
factors affect migration and invasion of nascent melanoma. To study migration of melanoma in vivo, I will
first optimize existing imaging pipelines in our lab to quantitatively to track cell migration by imaging of the
zebrafish skin. I can then assess the effect of knocking out keratinocyte-derived factors such as endothelin,
Wnt5A and BDNF using cell-type specific CRISPR-editing to determine their effects on migration. We
hypothesize that given the migratory role of these paracrine factors from in vitro data, we will see reduced
melanoma migration and invasion into adjacent tissues on migration tracking and histology by knocking-out these
factors in keratinocytes. By characterizing the role of tumor-associated keratinocytes in the melanoma
microenvironment, this proposal seeks to understand how melanoma modifies its microenvironment to overcome
its natural growth restraints and identify new targets to limit melanoma progression.

## Key facts

- **NIH application ID:** 10440282
- **Project number:** 5F30CA265124-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Yilun Ma
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $50,175
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440282

## Citation

> US National Institutes of Health, RePORTER application 10440282, In vivo characterization of keratinocytes in the melanoma microenvironment (5F30CA265124-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440282. Licensed CC0.

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