# Cellular and Metabolic Dysfunction in Sepsis-Induced Immune Paralysis

> **NIH NIH K23** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $196,020

## Abstract

PROJECT SUMMARY
Sepsis-induced immune paralysis (IP) is associated with consequential and often long-term effects including
susceptibility to secondary and opportunistic pathogens, and persistent immune disturbances that may culminate
in low-grade inflammation and death. Alterations in immune cell metabolism and impaired cell signaling are
pathophysiologic features of sepsis-induced IP. There is a strong scientific premise supporting the influential role
of fatty acids (FA) and their acyl carnitine (AC) metabolites in cellular energy metabolism, immune signaling, and
modulation of cytokine release. These concepts highlight the potential role of metabolites as active contributors
to disease pathophysiology rather than solely representing consequences of underlying pathways. To address
this paradigm, Lisa Torres, MD, MS, proposes this career development award with the overall objective to
characterize metabolic and protein biomarkers of septic IP relative to the most widely accepted surrogate biomarker
of IP, CD14+ monocyte HLA-DR expression. With the assistance of a multi-disciplinary mentoring team, Dr.
Torres proposes the following Aims in a cohort of critically septic and non-septic patients, stratified by presence
or absence of IP: (1) determine the relationship between dysregulated FA metabolism and sepsis-induced IP;
(2) characterize the role of immune paralyzed response proteins (IPRPs) as cellular mediators and candidate
biomarkers associated with sepsis-induced IP; and (3) explore the effect of IP as a mediating variable between
sepsis and patient outcomes. In Aim 1, Dr. Torres will measure fatty acid oxidation (FAO) utilization and perform
metabolic tracing with 13C-FAs to assess AC synthesis in PBMCs from recruited patients (N=280). In Aim 2, Dr.
Torres will use a THP-1 monocyte-like cell line and patient PBMCs (Aim 1) to determine the impact of IPRP
agonists on cellular activation. She will also measure IPRPs in plasma of recruited patients (Aim 1). In Aim 3,
Dr. Torres will use causal inference methods to estimate the effect of IP as a mediator on the causal pathway
between sepsis and adverse patient outcomes. Dr. Torres's long-term career goal is to become an independent
researcher in sepsis translational investigation and molecular epidemiology, engaged in understanding
endotypes and mechanisms that drive pathogenesis amongst critically ill patients. In this career development
award, her goals are to gain focused training in FA metabolism; become proficient in immune cell signaling
pathways of inflammation and inhibition of activation; develop skills to design, recruit and retain a cohort of
critically ill subjects to explore the clinical relevance of patient characteristics and sepsis-induced IP on outcomes
using causal inference methods; and build expertise in statistical analysis of complex biological data. She will
accomplish this through mentoring, coursework, dissemination of research, and hands-on-experience, all
necessary fo...

## Key facts

- **NIH application ID:** 10912771
- **Project number:** 5K23GM151730-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lisa Kristina Torres
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,020
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912771

## Citation

> US National Institutes of Health, RePORTER application 10912771, Cellular and Metabolic Dysfunction in Sepsis-Induced Immune Paralysis (5K23GM151730-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10912771. Licensed CC0.

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