# Visualizing cell dormancy in a Her2 Crainbow model of breast cancer metastasis > **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $178,889 ## Abstract Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 24-029. Dr. Snyder’s OMF R01, “Visualizing tumor heterogeneity in an immune intact and autochthonous mouse model of breast cancer” has approximately two years remaining on the award. The objective of this parent award, is to recapitulate the genetic heterogeneity of HER2 oncogenes in a genetically tractable model more closely resembling the human condition – including an intact immune system and stromal network. Our approach has been to validate a Cancer rainbow (Crainbow) mouse model of HER2+ breast cancer to visualize wildtype (WT), the splice-isoform exon 16 null isoform (d16), and the N-terminally truncated null isoform (p95). The parent R01 award is broadly demonstrating heterogeneity of tumor cell states, immune responses, fibroblast cross-talk, and the effects of HER2-targeted therapy. New preliminary data show that HER2 Crainbow isoforms differ in their metastatic potential and their primary tumor cell lines are also associated with distinct dormancy states including expression of the dormancy marker, NR2F1. Additional, preliminary support shows that the HER2 Crainbow cell lines differ in their intrinsic ability to evade the immune system. This collaborative supplement supports testing the hypothesis that p95 cells express gene signatures characterized by NR2F1 dormancy and Nectin2 immune checkpoint to promote metastatic potential and immune escape of dormant tumor cells. Two specific aims are proposed that will in (Aim 1) Determine the role of NR2F1 overexpression in dormancy and dissemination of p95 HER2 expressing tumor cells and in (Aim 2) Determine a role for Nectin2/3 in promoting immune escape in dormant p95 tumor cells. Dr. Bravo-Cordero’s expertise is necessary for the proposed intravital imaging studies and his expertise in tumor dormancy signaling. Already, our team has initial studies and established Crainbow cell lines and Crainbow mouse models at Dr. Bravo-Cordero’s laboratory. Therefore, the proposed supplement is already “shovel-ready” and has a high likelihood of success. The expected outcome of this supplement is three-fold: i) The supplement will continue to validate the HER2 Crainbow modeling technology as an important tool for visualizing tumor heterogeneity in immune intact models. ii) The supplement will also provide necessary resources for continuing to foster an early collaborative relationship between Drs. Snyder and Bravo-Cordero by providing time and funds to complete a manuscript and then apply for subsequent collaborative project grants. iii). The supplement will also provide important funding for demonstrating a new molecular mechanism that induces dormancy and promotes immune escape. Overall, this will provide an exciting strategy for promoting immune recognition of dormant tumor cells and thereby preventing or treating metastatic cancers. ## Key facts - **NIH application ID:** 11068362 - **Project number:** 3R01CA255372-04S4 - **Recipient organization:** DUKE UNIVERSITY - **Principal Investigator:** Joshua Clair Snyder - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $178,889 - **Award type:** 3 - **Project period:** 2021-02-09 → 2026-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11068362 ## Citation > US National Institutes of Health, RePORTER application 11068362, Visualizing cell dormancy in a Her2 Crainbow model of breast cancer metastasis (3R01CA255372-04S4). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11068362. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*