# The Study of Jag1-Notch in the Extravasation of Triple Negative Breast Cancer Cells in Metastasis.

> **NIH NIH F30** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $51,752

## Abstract

Project Summary
Triple negative breast cancer (TNBC) makes up to 15-20% of breast cancer diagnoses. While surgery and
adjuvant chemotherapy are effective treatment options for early-stage disease, there are very few therapeutic
options for advanced metastatic TNBC, and the 11% relative five-year survival rate highlights an urgent need to
discover actionable targets. In the hematogenous metastatic cascade, a few aggressive tumor cells are capable
of crossing the endothelial barrier at least twice: when entering systemic circulation (intravasation) and then
again when exiting circulation to colonize distant organs (extravasation). High expression of JAGGED-1 (JAG1),
a Notch ligand, is strongly associated with TNBC metastasis and consequent mortality. Our preliminary work in
static culture suggests that JAG1 enhances TNBC binding to the endothelium and transendothelial migration
(TEM), thereby promoting dissemination of tumor cells through vascular beds. We propose to study two distinct
mechanisms for JAG1 in the metastatic cascade. In Aim 1, we will investigate how tumor JAG1 signals in trans
to the endothelium to prime the vascular barrier for invasion. We will examine extravasation of our recently
generated TNBC CRISPR JAG1 knockout clones and control cells using a microfluidics system that faithfully
models capillary fluid shear forces and permits visualization of multiple critical steps of extravasation in vitro. We
will also test the role of JAG1 in vivo by examining the rate of lung capillary extravasation and pulmonary seeding
following tail vein injection of JAG1 knockout and control TNBC cells. In Aim 2, we will define the tumor cell-
intrinsic transcriptional program regulated by JAG1. Our preliminary RNA sequencing data suggest that novel
JAG1 targets promote cell surface interactions distinct from Notch targets. We will determine the metastatic
importance of key JAG1 targets by restoring expression and testing for TEM phenotypes. In the training plan of
the fellowship, I highlight an integrated scientific, clinical, and educational blueprint to enhance my personal
research and doctoring skills as an aspiring physician-scientist in oncology.

## Key facts

- **NIH application ID:** 10556318
- **Project number:** 5F30CA257269-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Benjamin Gordon
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-09-16 → 2025-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556318

## Citation

> US National Institutes of Health, RePORTER application 10556318, The Study of Jag1-Notch in the Extravasation of Triple Negative Breast Cancer Cells in Metastasis. (5F30CA257269-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10556318. Licensed CC0.

---

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