# Protein tyrosine phosphatase non-receptor 14 in vascular stability and remodeling

> **NIH HL R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2026 · $699,899

## Abstract

ABSTRACT
The vascular system is critical to life, infusing each organ of the body with oxygen and nutrients, and
transporting and interacting with immune cells that protect the body. In the adult, maintenance of an intact
vascular endothelium is under strict homeostatic control to prevent edema or hemorrhage. Wounding or tissue
hypoxia can result in angiogenesis and vascular remodeling. The process of vascular homeostasis is highly
regulated and involves many molecular players acting in concert. Under disease conditions, orchestration of
these molecular processes may go awry. This is especially true in rare Mendelian disorders that are caused by
mutations in key components of this machinery, such as Hereditary Hemorrhagic Telangiectasia (HHT), which
is caused by loss of function mutations in ENG, ACVRL1, or SMAD4. Understanding the molecular
underpinnings that regulate vascular homeostasis is critical to many diseases, including susceptibility to, and
recovery from, acute lung injury and COVID-19. Here, we will investigate the role of protein tyrosine
phosphatase non-receptor, type 14 (PTPN14) as a critical player in regulation of both blood and lymphatic
vessel homeostasis. We previously showed that genetic variation within the PTPN14 gene associates with
pulmonary arteriovenous malformations (AVMs) in HHT patients, and human genetics studies suggest a role
for PTPN14 in lymphatic development and homeostasis. PTPN14 is an antagonist of YAP signaling and we
have shown that it supports ALK1(ACVRL1)/SMAD4 signaling. We have identified several cis-eQTL in the
PTPN14 gene that associated with PTPN14 expression and with the presence of pulmonary AVM in HHT,
suggesting that PTPN14 expression levels influence AVM incidence. We have also identified two rare non-
synonymous PTPN14 SNPs that segregate with AVMs and we will also determine how these affect PTPN14
function and molecular interactions with SMAD4 and YAP/TAZ. We will use human engineered microvessels
under flow con

## Key facts

- **NIH application ID:** 11289446
- **Project number:** 5R01HL164891-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ROSEMARY J AKHURST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $699,899
- **Award type:** 5
- **Project period:** 2023-03-15T00:00:00 → 2027-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11289446

## Citation

> US National Institutes of Health, RePORTER application 11289446, Protein tyrosine phosphatase non-receptor 14 in vascular stability and remodeling (5R01HL164891-04). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11289446. Licensed CC0.

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