# Gas6 regulation of premalignant mammary cells

> **NIH NIH F31** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $45,520

## Abstract

PROJECT SUMMARY
Ductal carcinoma in situ (DCIS) is the most common form of pre-invasive breast cancer, accounting for 30% of
all diagnosed breast cancers. Clinical evident estimates that ~40% of patients with DCIS left untreated will
progress to invasive breast cancer. Although, the mechanisms by which pre-invasive DCIS cells acquire the
ability to invade the adjacent stroma are largely unknown. The long-term research goals of these studies are to
understand the molecular switch that occurs when pre-invasive lesions break through the basement membrane
to invade the surrounding stroma. The proposed studies aim to dissect the role of macrophages in
premalignancy and to identify the mechanisms that promotes tumor invasion into the stroma. Using mouse
models of early progression, we have shown that macrophages are recruited to pre-invasive lesions and
polarized toward a tumorigenic phenotype, and secret the cytokine Gas6. Our hypothesis is that macrophages
exert distinct functions at different stages of premalignancy, and macrophage-derived Gas6 promotes the
transition to invasive cancer. This hypothesis will be tested by the following aims: Aim 1: To characterize
macrophage phenotypes in pre-invasive lesions and determine whether their function is dependent on Gas6.
Aim 2: To determine the contribution of stromal-derived Gas6 on the progression of early stage lesions. Our
studies will utilize several mouse models, a unique 3-D culture system, and single cell RNA-seq to dissect the
role of macrophage-derived Gas6 in the progression of premalignancy. By understanding the mechanisms of
invasion, this study could identify biomarkers to be used in therapeutics to predict patient outcome and direct
treatment. The results of this study will significantly enhance our understanding of DCIS biology and early
stage breast cancer progression. Through the course of this fellowship I will learn indispensable techniques,
enhance my writing and presentation skills, and fine tune my critical thinking skills. I have formed a strong
mentoring committee to help fill in the gaps in my scientific career. I will receive training in mouse models,
breast cancer biology, human and mouse pathology, and bioinformatics, all of which will prepare me for the
next stage of my career. I have access to a highly collaborative, breast cancer-rich research environment,
comprised of basic scientists, clinicians, translational scientists, and epidemiologist. There are excellent core
facilities from multiple universities and institutions within close proximity. There are many opportunities to
participate in professional development workshops, as well as attend outstanding seminars and scientific
retreats. My sponsor, co-sponsors and I have devised specific career development sessions that will enhance
my training, facilitate new collaborations, and play an integral role in developing into a leading, independent
researcher.

## Key facts

- **NIH application ID:** 9925044
- **Project number:** 5F31CA239445-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Michelle D. Rojo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925044

## Citation

> US National Institutes of Health, RePORTER application 9925044, Gas6 regulation of premalignant mammary cells (5F31CA239445-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925044. Licensed CC0.

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