# CORE D - Proteomics Core

> **NIH NIH P01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2022 · $589,485

## Abstract

SUMMARY
The Proteomics Core facility (Core D) will support the proposed projects to address the central hypothesis of the
program; protein glycosylation and glycoprotein remodeling alter the coagulopathy and inflammation of sepsis.
Core D uses state-of-the-art mass spectrometry to analyze plasma and cellular proteomes in sepsis. Core D has
made essential contributions to the progress of the P01 during the first funding cycle, providing important findings
in support of all three research projects, and findings that led to two publications, one in Nature Communications.
The Specific Aims of Core D are to: 1) Assess time and pathogen-dependent changes to the Plasma Proteome
resulting from sepsis, 2) Characterize the time and pathogen-dependent remodeling of the vascular surface
proteome, and 3) Determine the molecular basis of enhanced consumption coagulopathy exhibited during Gram-
negative sepsis.
Aim 1 focuses on plasma proteomics for all three projects. Project 1 will use plasma proteomics to identify
specific glycosidases, their glycoprotein substrates, and endocytic lectin receptors and determine their impact of
their homeostatic regulation on the coagulopathy and inflammation of sepsis. Project 2 will use plasma
proteomics to identify components and mechanisms of both the pathogen and host determining virulence and
sepsis pathogenesis and determine their utility in the stratification and prognosis of experimental and human
sepsis. Project 3 will use plasma proteomics to determine vascular surface marker shedding into circulation in
murine models of sepsis, and their impact in the coagulopathy and inflammation of sepsis while identifying
mechanistic links that may enable human disease stratification and prognosis.
Aim 2 focuses on characterizing the vascular surface proteome in support of Project 3. This work will characterize
organ-specific changes to vascular cell surface proteomes and determine their impact in the coagulopathy and
inflammation of sepsis and their utility in the stratification and prognosis of human disease.
Aim 3 will support Project 2 in seeking to characterize the enhanced consumption coagulopathy exhibited during
Gram-negative sepsis. This work will use activity-based proteomics and standard protein fractionation analysis
to identify bacterial function(s) responsible for the observed FXI-stimulatory activity present in SC/ST/EC
supernatants; and determine its role in the elevated consumption coagulopathy in Gram-negative sepsis and
possible utility in the stratification and prognosis of human disease.

## Key facts

- **NIH application ID:** 10475596
- **Project number:** 5P01HL131474-07
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Jeffrey W Smith
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $589,485
- **Award type:** 5
- **Project period:** 2016-07-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475596

## Citation

> US National Institutes of Health, RePORTER application 10475596, CORE D - Proteomics Core (5P01HL131474-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10475596. Licensed CC0.

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