# Deconstructing cellular heterogeneity and subpopulation cooperation in non-small cell lung cancer metastasis

> **NIH NIH R50** · EMORY UNIVERSITY · 2021 · $143,985

## Abstract

PROJECT SUMMARY/ABSTRACT
Metastasis is responsible for 90% of cancer deaths, yet there is a severe lack of effective anti-metastatic targeted
therapeutics. Collective invasion, where heterogeneous packs of cells travel together, is a major mode of
metastasis observed in patients across many solid tumor types. The underlying biological mechanisms for how
the collective invasion pack communicates to emerge, navigate, and persist as a single cohesive unit remain
unclear. Using our patented SaGA technique (Spatiotemporal Genomic and Cellular Analysis), which leverages
a combination of live-cell confocal microscopy and fluorescence-activated cell sorting, we found that cooperation
between leader and follower subpopulations is crucial for successful collective invasion, with leaders promoting
the invasion of followers, and followers promoting the survival and proliferation of leaders. The proposed work
deconstructing how the collective invasion pack facilitates metastasis will be performed by Dr. Janna Mouw in
the laboratory of Dr. Adam Marcus, the Unit Director, at the Winship Cancer Institute at Emory University. The
overall objective of the proposed work is to dissect the molecular underpinnings of subpopulation cooperation in
promoting collective invasion and metastasis as outlined in Dr. Marcus's funded R01 grants, R01CA236369 and
R01CA250422. As such, the goals of Dr. Mouw's project are to: 1) define how heterogeneous lung cancer
subpopulation cooperation and spatial coordination through Jag1 drive collective cancer cell invasion and tumor
metastasis, and 2) establish whether atypical angiogenic mimicry and leader cell-driven Jag1 signaling
destabilize the tumor endothelium to promote lung cancer transendothelial migration and metastasis. Dr. Mouw
has more than 15 years of experience in cancer research at top-tier institutions. She has a multidisciplinary
background in cancer biology, bioengineering, and mechanical engineering, bringing a unique expertise and
perspective to her research on the roles for subpopulation communication and collective invasion in cancer
progression and metastasis. Through these experiences, Dr. Mouw has extensive training using a vast variety
of in vitro and in vivo approaches to comprehensively test her hypotheses. Dr. Mouw has made significant
contributions to Dr. Marcus's research program, and has published multiple first-author articles in well-regarded
journals, such as Nature Medicine and Nature Cell Biology. Overall, Dr. Mouw has the expertise and dedication
to lead these studies, which will define the metastatic potential and translational impact of the rare, yet invasive
leader population in lung cancer patients. Taken together, the work proposed here will be of impactful benefit to
the research program, and provide critical mechanistic insight into the atypical angiogenic mimicry program and
translational value towards targeting lung cancer patient leader cell biology.

## Key facts

- **NIH application ID:** 10323872
- **Project number:** 1R50CA265345-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Janna K Mouw
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $143,985
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323872

## Citation

> US National Institutes of Health, RePORTER application 10323872, Deconstructing cellular heterogeneity and subpopulation cooperation in non-small cell lung cancer metastasis (1R50CA265345-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10323872. Licensed CC0.

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