# Bioanalytical Core

> **NIH NIH P01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $176,606

## Abstract

The overarching goal of this TPPG is to elucidate common pathogenic mechanisms of pulmonary arterial
hypertension (PAH) and target these pathways with novel drug strategies. To that end, the initial TPPG
funding period identified perturbations in several NO-based signaling pathways that contribute to PAH
pathogenesis. Further, it identified and developed a number of promising candidate therapeutics. The current
project focuses specifically on two candidate therapeutics - oral nitrite (NO2-) and nitro-oleic acid (NO2-OA) –
and their ability to modulate NO signaling to prevent PAH progression and heart failure. Crucial to the success
of this project is the ability to specifically and accurately measure NO, its metabolites, and its protein/lipid
signaling targets. To that end, the Bioanalytical Core brings together existing infrastructure and expertise to
support investigators across all three projects in detecting and quantifying NO/reactive species that participate
in seminal signaling events in biological samples and in vivo models. Specifically, the core is comprised of
three critical components that will synergize to comprehensively detect and quantify all pertinent reactive
nitrogen (NO, nitrite, nitrate, S-nitrosothiol, nitrated lipids) and reactive oxygen (superoxide, hydrogen peroxide,
lipid radicals) species in both bench and bedside projects. 1) The chemiluminescence core will utilize
reductive chemistry in conjunction with chemiluminescence NO detection to measure NO and its metabolites in
biological specimens and assess bacterial nitrite/nitrate reductase activity in the microbiome. 2) The EPR
component will utilize cutting edge EPR technology with spin trapping to directly measure radicals in biological
samples. Additionally, EPR technology will enable the differentiation of endogenous and 15-N labeled NO
species in biological samples. 3) The Mass Spectroscopy component will enable the measurement of NO and
oxo-modified lipid and protein biomolecules. All three components of the Bioanalytical Core are already
optimized for human and animal samples and are directed by experts in the respective technologies.
Collectively, the services offered by the Bioanalytical Core will greatly expand and refine the ability of
researchers in all three research projects of this TPPG to elucidate novel NO pathways and develop unique
therapeutics that work mechanistically through the modulation of NO signaling.

## Key facts

- **NIH application ID:** 9939659
- **Project number:** 5P01HL103455-10
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sruti Shiva
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,606
- **Award type:** 5
- **Project period:** 2011-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939659

## Citation

> US National Institutes of Health, RePORTER application 9939659, Bioanalytical Core (5P01HL103455-10). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9939659. Licensed CC0.

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