# Aminopeptidase N Driven Signaling in the Development of Pulmonary Hypertension

> **NIH NIH K99** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $102,403

## Abstract

PROJECT SUMMARY/ABSTRACT
CANDIDATE: Dr. James's career objective is to establish an independent research group investigating
mitochondrial dysfunction (MD) and Aminopeptidase N (APN) driven signaling in pulmonary hypertension (PH).
The overall research and career development plan is carefully crafted to impart the necessary skills for Dr. James
to establish a novel and independent line of research. The plan includes the following objectives: 1) gain
additional training in research methodology and professional development; 2) developing strong publication
records; 3) presenting his work at scientific meetings to make an impact on the field 4) obtaining preliminary data
for his first independent grant. ENVIRONMENT: The primary mentor Dr. Rafikov is an expert in mitochondrial
dysfunction and PH. He will provide guidance and technical expertise for aspects in all aims. Co-Mentor Dr.
Vinicio de Jesus Perez is an expert in pericyte biology and PH and will train Dr. James in pericyte isolation, co-
culture, and data analysis. Co-mentor Dr. Ralph Fregosi is an expert electrophysiologist and will extensively
prepare Dr. James in his career development in addition to training with patch clamp techniques. All the mentors
with the rest of the advisory committee will ensure the success of Dr. James's proposal. All the proposed work
will be carried out in Dr. Rafikov's laboratory with training gained from labs of Dr. de Jesus Perez and Dr. Zhiyu
Dai for single cell transcriptomics. Dr. Rafikov has all the necessary funding from NIH and other sources to
support Dr. James during the K99 training phase. The Department of Medicine at the University of Arizona has
excellent facilities and supportive faculty members and provides a nurturing environment for the training phase.
RESEARCH: The overarching hypothesis is that MD triggers the overexpression of the protein, APN in pericytes.
APN has been shown to cause migration, invasion, and proliferation of cells. Preliminary data suggests that MD
in rats triggers an increase in pericyte APN, causing them to dissociate from endothelial cells (EC's) in capillaries,
transform into smooth muscle-like cells (PASMC) and proliferate. This ultimately leads to vascular remodeling
and PH. Three specific aims will address this hypothesis. Aim 1: To Investigate the role of APN in pericyte-EC
communication and pericyte transformation to PASMC. Aim 2: To Investigate the role of MD on APN expression
and signaling. Aim 3: To Verify the impact of blocking APN and reversing MD on vascular remodeling in PH.
The study will utilize several techniques including single cell transcriptomics, 3D imaging and co-culture to
address these questions. The results of this study will lead to a better understanding of how MD drives APN
expression and signaling. This could define novel targets in the treatment of PH for favorable clinical outcomes.
The proposed training will enable Dr. James to acquire new experimental skills and execute his research pla...

## Key facts

- **NIH application ID:** 10784461
- **Project number:** 1K99HL171869-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Joel James
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,403
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784461

## Citation

> US National Institutes of Health, RePORTER application 10784461, Aminopeptidase N Driven Signaling in the Development of Pulmonary Hypertension (1K99HL171869-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10784461. Licensed CC0.

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