# Aspirin and Novel Lipid Mediators in Nonalcoholic Fatty Liver Disease

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $199,383

## Abstract

PROJECT ABSTRACT
The candidate, Dr. Tracey Simon, is an accomplished clinical research fellow at the Massachusetts General
Hospital, with training in gastroenterology and hepatology. Her long-term career goal is to become an
independent physician-investigator, with a patient-oriented clinical research program devoted to nonalcoholic
fatty liver disease (NAFLD) and steatohepatitis (NASH). To achieve this, she has developed a detailed and
integrated career development plan, designed to provide focused training to achieve her short-term career
goals: 1) to gain experience in pharmacoepidemiology and large database research; 2) to acquire skills in the
analysis of metabololipidomics data, for biomarker development; 3) to build proficiency in the conduct of clinical
trials; 4) to obtain the necessary skills, experience and preliminary data to produce a successful R01 application.
Experimental and clinical data show that unresolved inflammation is a key hallmark of NASH, the aggressive
and inflammatory form of NAFLD. As proof of this principle, anti-inflammatory drugs like aspirin have been shown
in vivo to resolve NASH and attenuate fibrosis. This benefit was previously attributed to the inhibition of pro-
inflammatory eicosanoid lipid synthesis. However, it was recently discovered that aspirin also stimulates the
production of novel anti-inflammatory eicosanoid lipid mediators, called specialized proresolving mediators
(SPMs). Based on preclinical studies and the candidate’s preliminary data, we hypothesize that NASH reflects
a state of relative SPM deficiency, and that aspirin may resolve NASH and improve hepatic outcomes through
pathways governed by SPMs. In Aim 1, we will use nationwide Swedish registers to define the impact of aspirin
use on risk for incident HCC and liver-related death, in patients with biopsy-proven NAFLD. In Aim 2, we will
use banked serum and liver pathology data from two independent cohorts, to measure a validated panel of ~65
targeted SPMs, using a state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS-MS) platform,
and we will define and validate a diagnostic SPM signature for NASH. In Aim 3, we will conduct a pilot
randomized controlled trial to assess the preliminary efficacy of low-dose aspirin on NASH regression. Dr. Simon
is supported by a multidisciplinary mentorship team of renowned scientists and advisors in Hepatology,
pharmacoepidemiology, eicosanoid biology, biomarker discovery and NAFLD clinical trials, to guide her path to
scientific independence. She will train in the outstanding scientific environment of the MGH Fatty Liver Clinic,
the Harvard School of Public Health and the Karolinska Institute. Completing this project will provide her with
preliminary data towards a future biomarker-guided aspirin interventional trial, for patients with NASH. With this
foundation, Dr. Simon will launch her independent clinical research career, using advanced lipidomics and
pharmacoepidemiologic tools to imp...

## Key facts

- **NIH application ID:** 9999580
- **Project number:** 5K23DK122104-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tracey Simon
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,383
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999580

## Citation

> US National Institutes of Health, RePORTER application 9999580, Aspirin and Novel Lipid Mediators in Nonalcoholic Fatty Liver Disease (5K23DK122104-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999580. Licensed CC0.

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