# Implementing Photodissociation Mass Spectrometry to study Disease and Lipid Structure

> **NIH NIH F31** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $36,631

## Abstract

Abstract
Lipids fulfill an array of cellular functions by composing cellular membranes, engaging in signaling pathways,
and modulating protein structure. Disruptions in carefully regulated lipid compositions perturb cellular function
and correlate with cancer, neurodegeneration, diabetes, and cardiovascular disease. The correlation between
aberrant lipid composition and disease has inspired lipid profiling as a powerful diagnostic tool. Analysis of
structural changes that concur with disease promises to reveal highly specific biomarkers and insight into the
disease development. This proposal focuses on the development of ultraviolet photodissociation (UVPD) tandem
mass spectrometry approaches for the characterization of glycerophospholipids (GPL) and the cardiolipin (CL)
subtype in cancerous tissue. Cancer induces a stark metabolic shift that significantly affects lipid metabolism.
UVPD is a high-energy ion activation technique used for MS/MS analysis, informing subtle features that are not
captured by other mass spectrometry methods. Implementing UVPD to track changes in tumorous GPL
structures with fine detail offers an avenue to explore the full effects of cancer on lipid dysregulation. The
objectives of this proposal include: Aim 1: Development of an LC-MS-UVPD workflow to identify changes in
phospholipid structure between breast cancer tissue subtypes. A quantitative lipidomic workflow incorporating
UVPD will be developed for the high-throughput analysis of GPL isomers. The proposed strategy will be applied
to analyze a cohort of breast tumor lipid extracts and identify significant structural changes and prognostic
biomarkers. Aim 2: Complete characterization of cardiolipins from cancer cells using UVPD. CLs are of particular
relevance for cancer research but present challenging structures. UVPD is the only activation method reported
to provide detailed CL characterization and will be expanded upon to characterize CLs from tumorous tissue. All
together, the proposed strategies promise avenues to identify diagnostic biomarkers, potential therapeutic
targets, and disease mechanisms. Importantly, these strategies would be applicable for lipidomic analyses of
GPLs and CLs from other diseases.

## Key facts

- **NIH application ID:** 10141856
- **Project number:** 1F31CA257404-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Luis A Macias
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,631
- **Award type:** 1
- **Project period:** 2021-03-10 → 2024-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141856

## Citation

> US National Institutes of Health, RePORTER application 10141856, Implementing Photodissociation Mass Spectrometry to study Disease and Lipid Structure (1F31CA257404-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141856. Licensed CC0.

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