# NYULH Metastasis Research Network Center (NYULH MetNet Center)

> **NIH NIH U54** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $1,688,223

## Abstract

OVERALL SUMMARY
Conventional views of cancer as a predominantly genetic disease that proceeds in a step-wise, linear manner,
have ceded to an understanding that tumor progression involves a multifaceted set of tumor cell-intrinsic and
micro-environmental adaptations that co-evolve dynamically and non-linearly. However, much remains to be
discovered about how different cell populations in the local environment drive metastatic behavior at different
stages of tumor progression. Primary melanomas that are only millimeters thick can disseminate to lymph nodes
and distant organs. This clinical feature suggests that egress of tumor cells from a primary site occurs early in
melanoma development making melanoma an exceptional model to study these dynamic adaptations during the
earliest stages of tumor progression. Our central hypothesis is that melanoma metastasis is driven by a
combination of tumor cell–intrinsic features and interactions with micro-environmental compartments
that govern early dissemination and immune evasion in the regional draining lymph nodes. To test this
hypothesis, we propose three inter-related projects, supported by three cores that will collectively build an in-
depth transcriptional and cellular map of critical compartments in the tumor microenvironment during early
melanoma dissemination, in both mouse models and patient biospecimens. Successful completion of these
projects will identify genes and transcriptional programs within those compartments that drive and maintain
tumorigenic adaptations and ultimately metastatic dissemination. Our aims are to: 1. Map the cellular and
molecular evolution of primary melanomas and their local and regional microenvironments to identify critical
‘switches’ that drive non-linear tumor progression; 2. Mechanistically dissect the emergence and functional
relevance of transcriptionally defined cell state heterogeneity of malignant and non-malignant cell populations;
3. Identify novel therapeutic vulnerabilities to intercept early dissemination, mobilize systemic immune
surveillance, and improve patient outcomes; and 4. Leverage the information gained to define new biomarkers
of melanoma metastasis. We expect that knowledge generated through our approach may define new
biomarkers of melanoma metastasis and therapeutic strategies to manage early disease. Our approach can
serve as a roadmap to study early tumor progression at an unprecedented level of cellular, spatial and temporal
resolution. It will provide a comprehensive picture of interactions both within the tumor microenvironment and
tumor draining lymph nodes that influence tumor cell behavior and condition the host to be receptive to metastatic
spread. We will leverage the complementary and synergistic expertise of our research team with an established
record of productive collaboration, our novel genetically engineered mouse model that recapitulates early
progression of human melanoma, and our access to high quality, clinically annotate...

## Key facts

- **NIH application ID:** 10414442
- **Project number:** 1U54CA263001-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Eva Hernando
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,688,223
- **Award type:** 1
- **Project period:** 2022-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414442

## Citation

> US National Institutes of Health, RePORTER application 10414442, NYULH Metastasis Research Network Center (NYULH MetNet Center) (1U54CA263001-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414442. Licensed CC0.

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