# Translational Metabolomics in Critical Care

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $382,707

## Abstract

Sepsis and other critical illnesses remain significant hazards to human health. Sepsis is particularly challenging
because it is associated with great heterogeneity that has kept the identification of diagnostic and predictive bi-
omarkers and effective pharmacotherapy elusive. Adverse drug reactions are among the top six leading cause
of morbidity and mortality in the nation. To tackle these problems, my research program employs Translational
Metabolomics which bridges the translational gap between analytical and experimental techniques and the
clinical application of the science of metabolomics. Specifically, it is aimed at applying metabolomics to: 1) in-
crease understanding of the metabolic processes that underlie clinically challenging problems like sepsis; and
2) improve prediction of drug response (pharmacometabolomics), including adverse drug reactions. We have
an innovative swine model of sepsis that faithfully recapitulates the human situation, novel point-of-care (POC)
technology and can assay biospecimens using a range of analytical platforms including liquid chromatography
(LC)-mass spectroscopy (MS) and quantitative nuclear magnetic resonance (NMR). Our recent progress has
led to paramount findings about the mechanisms that underlie sepsis responsiveness to L-carnitine, metabolic
adaptiveness and adverse drug reactions. Our pharmacometabolomics approach introduced the idea of meta-
bolic provocation to identify latent sepsis phenotypes. We have also determined that blood carnitine concentra-
tions serve as a signal of metabolic stress that may predispose to adverse drug reactions. Under this MIRA
(R35) application, the overarching and long-term goal of my program is to move metabolomics from knowledge
discovery to implementation that will drive the transformation of the care of patients with critical illnesses. To
achieve this, we will address three key gaps in knowledge: 1) The metabolic crisis timeline of critical illnesses
like sepsis is, and its trajectories are, poorly understood; 2) there is limited understanding of the mechanistic
underpinnings that contribute to metabolic adaptiveness and flexibility in sepsis; and 3) there is an absence of
fundamental understanding of the metabolic mechanisms that underlie the variance in drug response including
adverse drug reactions. With the assistance of productive, ongoing collaborations with an analytical chemist
and bio-informaticist, we expect this work will bring about a paradigm shift in the understanding of the mecha-
nistic underpinnings of sepsis and drug response. Long-term, we expect that the found sepsis-induced meta-
bolic defects, evidenced by altered carnitine and acyl-carnitine profiles, will lead to the identification of new
drug target opportunities, diagnostic and prognostic biomarker candidates and new POC technology that will
drive the early, reliable detection of sepsis. In addition, we will have new insights into the mechanisms that di-
rect and differentiate dru...

## Key facts

- **NIH application ID:** 10116432
- **Project number:** 5R35GM136312-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** KATHLEEN A STRINGER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,707
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116432

## Citation

> US National Institutes of Health, RePORTER application 10116432, Translational Metabolomics in Critical Care (5R35GM136312-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116432. Licensed CC0.

---

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