# Role of the Alternative Complement Cascade in Connective Tissue Disease Associated Pulmonary Arterial Hypertension (CTD-PAH)

> **NIH NIH R03** · UNIVERSITY OF ROCHESTER · 2020 · $77,000

## Abstract

Abstract
This revised R03 award will assess the novel hypothesis that the alternative complement pathway is a critical
mediator and potential therapeutic target for connective tissue disease associated pulmonary arterial
hypertension (CTD-PAH). This work will allow Dr. Benjamin Korman, a current NIAMS K08 awardee, to
develop a new area of research and develop independence. The studies described build upon exciting
preliminary data characterizing TNF transgenic mice (TNF-Tg) as a novel model of CTD-PAH. Specific aim 1
assesses the ability of genetic ablation of complement to prevent the PAH phenotype by crossing TNF-Tg mice
with complement component 3 (C3) deficient mice. To determine the specificity of this effect to CTD-PAH, the
effect seen will be compared to WT and C3 deficient mice with pulmonary hypertension induced by the Sugen-
hypoxia model. Specific aim 2 will further explore complement’s mechanistic role to assess how TNF and
complement in pulmonary artery endothelial cells regulate adhesion molecules and apoptosis, whether
classical or alternative complement factors are required for these phenotypes, and assess how endothelial cell
derived complement may alter macrophage phenotypes. In specific aim 3, we will use fusion-protein
complement inhibitors CR2-Crry (pan-complement) and CR2-fH (alternative pathway specific) to assess
whether treatment of TNF-Tg mice with complement inhibition can reverse established PAH and whether this is
specific to the alternative pathway. This proposal will provide critical preliminary data which will form the basis
for an R01 award in which Dr. Korman will study the pathological role of the complement cascade in CTD-PAH
and associated vasculopathy using patient materials and animal models.

## Key facts

- **NIH application ID:** 10041913
- **Project number:** 1R03AR075866-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Benjamin Douglas Korman
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041913

## Citation

> US National Institutes of Health, RePORTER application 10041913, Role of the Alternative Complement Cascade in Connective Tissue Disease Associated Pulmonary Arterial Hypertension (CTD-PAH) (1R03AR075866-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10041913. Licensed CC0.

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