# Center for Systems-level Study of Metastasis

> **NIH NIH U54** · ROCKEFELLER UNIVERSITY · 2024 · $1,557,708

## Abstract

Project Summary: Metastatic disease is a complex, dynamic and emergent process that requires collective and
coordinated interactions between many cell types, metabolites and the host. There is substantial clinico-
pathologic and experimental evidence for critical roles of neural innervation, lymphatic interactions, metabolites
and endothelial cells in regulating metastatic progression by altering cancer and immune cell functions. As such,
these cellular interactions likely shape metastatic progression, responses to therapy and metastatic
dissemination. However, we have a limited understanding of how these components coordinately regulate
metastatic progression. This application describes a series of highly innovative multidisciplinary molecular, cell-
biological, metabolic, massively-parallel single-cell sequencing and organismal methods applied towards
defining the dynamic and emergent mechanisms by which neural cells, lymphatics, immune cells and metabolites
interact to coordinately regulate metastatic progression—contributing to a systems-level understanding of
metastasis. We aim to (i) define the role of neural innervation on metastatic progression by characterizing neuro-
tumor and neuro-immune interactions and identifying neural signals and their pro-metastatic mechanisms of
action, (ii) determine how endothelial cells regulate innervation of metastatic tumors, (iii) define the role of
regionalized lymphatic interactions in driving metastatic progression and anti-metastatic immunity, (iv) assess
the role of neuro-immune and neuro-epithelial interactions on early metastatic dissemination and colonization,
(v) identify metabolite and protein signals that drive metastatic colonization, (vi) discover tumoral transcription
factors and RNA-binding proteins that act downstream of neural and metabolic signals to drive emergent pro-
metastatic gene expression programs, and (vii) determine the impact of standard chemotherapy on these
diverse cellular interactions and metabolic determinants of metastatic progression. Our proposed MetNet Center
will enhance our understanding of how interactions and crosstalk between cancer cells with nervous system
cells, lymphatics, vasculature and immune cells enables emergence of metastatic disease. We will also assess
how therapy impacts specific cell-cell and metabolic interactions of metastatic cells and provide insights into the
impact of specific cellular interactions in the primary microenvironment on metastatic dissemination, including
early dissemination. These findings will generate an integrated, systems-level understanding of metastasis,
enabling development of a new generation of anti-cancer therapies that prevent critical emergent coordinated
pro-metastatic interactions.

## Key facts

- **NIH application ID:** 10909174
- **Project number:** 5U54CA261701-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Sohail F. Tavazoie
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,557,708
- **Award type:** 5
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909174

## Citation

> US National Institutes of Health, RePORTER application 10909174, Center for Systems-level Study of Metastasis (5U54CA261701-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909174. Licensed CC0.

---

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