# Spatial Profiling of Melanocytic Tumors and Their Microenvironment

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $80,500

## Abstract

Spatial profiling of melanocytic tumors and their microenvironment
Understanding tissue structure is fundamental for biological sciences and for distinguishing benign versus
malignant neoplasms, but histopathological assessment alone is inaccurate for the diagnosis of certain tumors,
including a subset of melanocytic neoplasms (melanocytic nevi and melanomas), resulting in diagnostic errors
and worsened patient outcomes. Therefore, novel biomarkers for the diagnosis of melanoma are needed. To
identify such markers, it is imperative to better understand the interaction between melanocytes and neighboring
keratinocytes, immune cells, and other components of the complex tumor microenvironment in nevi and
melanoma.
Nevi and early primary melanoma display intratumoral heterogeneity, often coupled with low cellularity and purity.
Therefore, the tumor-microenvironment interactions could be missed by bulk approaches or single-cell
sequencing of advanced/metastatic tumors only, which has been the focus of most prior studies. The goal of this
research is to build high-resolution spatial maps of gene expression of the tumor and its microenvironment in
morphologically preserved nevi and melanomas to identify novel diagnostic biomarkers.
The hypothesis is that melanocytic tumors and their microenvironments contain subpopulations of cells with
characteristic gene expression patterns that differ between nevi and melanoma. We hypothesize that some of
these differentially expressed genes are spatially confined and cell-type specific and could be used as potential
diagnostic markers. Our prior data demonstrated differences in CDK2 gene expression between melanocyte-
rich regions of nevi and melanoma. In Aim 1, we will assess spatial expression of CDK2 by
immunohistochemistry in a tumor panel of over 200 nevi versus melanoma, comparing it to proliferative markers,
as well as established melanoma biomarkers, including PRAME. In Aim 2, to identify novel biomarkers, we will
establish high-resolution spatial maps of gene expression of tumor and microenvironment subpopulations in nevi
versus melanoma by performing a spatial whole transcriptome analysis and a high-plex single-cell imaging. Top
differentially expressed genes in these subpopulations will be validated via immunohistochemistry in the tumor
panel described above.
This study improves current theoretical concepts by investigating tumor and microenvironment populations in
nevi and early primary melanoma – the common, yet previously understudied tumor types. Furthermore, this
study utilizes improved state-of-the-art approaches, including high-plex single-cell spatial gene expression
profiling. This research will improve the understanding of tumor-microenvironment subpopulations in their
spatially correct context, relevant for tumor biology and biomarker development, ultimately leading to improved
diagnostic accuracy of melanoma and improved patient outcomes.

## Key facts

- **NIH application ID:** 10876459
- **Project number:** 5R03CA277645-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Maija Helena Tuulia Kiuru
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $80,500
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876459

## Citation

> US National Institutes of Health, RePORTER application 10876459, Spatial Profiling of Melanocytic Tumors and Their Microenvironment (5R03CA277645-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876459. Licensed CC0.

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