# Characterizing the Role of Leucyl Aminoacyl tRNA Synthetase (LARS) in Breast Cancer Metastasis

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $51,036

## Abstract

PROJECT SUMMARY/ABSTRACT
 Breast cancer metastasis is a leading cause of mortality in US women. Despite advances in treatment
for patients with early stage tumors, prognosis remains poor for patients with metastatic disease. Prior work has
demonstrated a direct role for transfer RNAs (tRNAs) as drivers of breast cancer metastatic progression, through
differential abundance resulting in changes in cell proteomic landscape. I hypothesize that aminoacylation status,
as in, whether or not a tRNA is charged with an amino acid, and the requisite aminoacyl tRNA synthetase (aaRS)
responsible for tRNA charging, will also play a role in breast cancer metastatic progression. To test this
hypothesis, charged tRNAs were profiled across cells of differing metastatic potential, which identified key
reductions in leucine tRNA charging in cells of higher metastatic potential. Preliminary xenograft and syngeneic
mouse metastasis studies further identified leucyl aaRS (LARS), responsible for charging leucine tRNAs, as a
metastasis suppressor. In this proposal, I will examine and further characterize the role of LARS in cancer
metastasis. In Aim 1, I will further characterize the effects of LARS manipulation (1) through knockdown and
overexpression in xenograft and syngeneic cancer mouse models, and (2) through genetic knockout in mouse
models of breast cancer. In Aim 2, I will investigate (1) the cellular phenotype of metastasis suppression through
in vitro assays and (2) the mechanism of charged tRNA-mediated metastasis suppression through downstream
RNA sequencing analysis and ribosomal profiling. These proposed studies will fill a gap in literature: though
tRNAs play a role in cancer progression, molecules related to their biogenesis have yet to be identified as
therapeutically meaningful targets in cancer metastasis. Successful completion of these aims will lay the
groundwork for future therapeutic targets with novel mechanisms, in treating metastatic breast cancer.
 I am an MD-PhD student at the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD
program, completing the proposed aims in the lab of Dr. Sohail Tavazoie at Rockefeller University. Dr. Tavazoie,
along with my committee members Drs. Charles Rice, Ping Chi and Kivanc Birsoy, provide strong scientific
expertise, guidance and resources to ensure successful completion of the project. Together, we have taken
steps to ensure my training plan also allows for development of necessary verbal and written communication
skills as well as mentorship opportunities. My clinical mentors, Drs. Pamela Charney and Ping Chi, will offer
critical advice on maintaining clinical acumen as I transition towards completion of medical training and select
research-track residency programs in Internal Medicine. Successful completion of the proposed plan in this
stellar training environment will enhance my foundational knowledge of RNA biology and teach me skills in
cancer biology and mouse modeling, setting me sol...

## Key facts

- **NIH application ID:** 10071869
- **Project number:** 5F30CA247026-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Maria Christina Passarelli
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-12-09 → 2023-12-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071869

## Citation

> US National Institutes of Health, RePORTER application 10071869, Characterizing the Role of Leucyl Aminoacyl tRNA Synthetase (LARS) in Breast Cancer Metastasis (5F30CA247026-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10071869. Licensed CC0.

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