# Recognition of O-GlcNAc Modified Proteins Using Site-Specific Antibodies

> **NIH NIH R43** · GLYCOSCIENTIFIC, LLC · 2023 · $275,767

## Abstract

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by high
blood pressure (hypertension) in the arteries of the lungs (pulmonary artery) for no apparent
reason. PAH is a disease of pulmonary vascular endothelial dysfunction with nitric oxide (NO)
deficiency and dysregulated glucose metabolism/utilization. It is a heterogeneous disorder likely
to be comprised of overlapping syndromes with varying origins and pathobiologies that presents
with many phenotypes. The idiopathic form of pulmonary arterial hypertension (IPAH) is
progressive and results in the deterioration of cardiopulmonary function and premature death.
The mean age at diagnosis of IPAH is 50 years with a higher female to male ratio. Presently,
PAH is considered a vasculopathy, and metabolic dysregulation has emerged as a major area
of research in the pathobiology of the disease. These metabolic changes results in structural
and morphological changes within the lung vasculature and cause increased pulmonary artery
pressure and pulmonary vascular resistance, which lead to right ventricular failure. Our lab and
others have shown that IPAH patients exhibit altered levels of NO, O-GlcNAc, glucose
metabolism, and insulin resistance. The nature of the primary abnormalities that trigger and
perpetuate these characteristics remains unclear. Currently, all therapies in PAH target
vasodilators and vasoconstrictors pathways (e.g. NO deficiency). The future of IPAH therapies
depend on our ability to identify the new molecular targets within these pathways. However, the
tools available to understand the role of glycosylation in human health and disease are lacking.
In particular, highly specific antibodies that can recognize peptide specific sequences modified
by O-GlcNAc is needed to help us better understand the disease pathobiology and improve
treatment of pathologic phenotypes in IPAH. Here we propose to create the first antibodies to
allow the study researchers to investigate the role of O-GlcNAc in PAH. We anticipate that these
antibodies will help shed light on PAH disease mechanism(s), and potentially offer new
therapeutic approaches.

## Key facts

- **NIH application ID:** 10697563
- **Project number:** 1R43HL166086-01A1
- **Recipient organization:** GLYCOSCIENTIFIC, LLC
- **Principal Investigator:** Marla Popov
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $275,767
- **Award type:** 1
- **Project period:** 2023-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697563

## Citation

> US National Institutes of Health, RePORTER application 10697563, Recognition of O-GlcNAc Modified Proteins Using Site-Specific Antibodies (1R43HL166086-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10697563. Licensed CC0.

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