# Regulation of smooth muscle hyperplastic growth in pulmonary

> **NIH NIH K01** · TUFTS MEDICAL CENTER · 2020 · $172,000

## Abstract

Abstract
The goal of this K01 Mentored Career Development Award is to investigate the role of FoxM1 and the
contributions of PLK1 in the “out-of-control” proliferation of human pulmonary artery smooth muscle cells
(HPASMC) as research training towards independence for a PI. Vascular remodeling is a primary feature of
pulmonary arterial hypertension (PAH) which is a fatal disease with very limited effective treatments. The
pathology of the disease involves vascular cell proliferation resulting in thickening of the media and blockage of
the vessel lumen. We discovered that the increased proliferative activities of the PAH HPASMC is associated
with transcription factors, FoxM1 and p53, and cell cycle regulator polo-like kinase 1 (PLK1). To train towards
independence the PI will pursue this research endeavor by testing the hypotheses that hyperplastic growth in
PAH HPASMC is the consequence of upregulated FoxM1 and PLK1 activity. Aim 1 of this proposal is to
investigate the roles of FoxM1 and PLK1 in the dysregulated proliferative behavior of HPASMC from PAH
patients and mouse PASMC derived from mice exhibiting hypoxic PH. This approach will use siRNA
knockdowns, lentivirus transduction of overexpressed wild-type or dominant negative forms of FoxM1 or PLK1
and implementation of targeted cell permeable peptides (CPP) in PASMC. Aim 2 will extend the studies on
PASMC in culture into in vivo studies using mice exposed to hypoxia/SU5416 PH model. This will allow for an
in vivo assessment of observations obtained from the human cells. In animal experiments the PI will use a
strategy of a “homing” peptide which is conjugated to a CPP, ensuring its delivery to target tissue. The PI will
apply targeted CPP against molecules determined critical from Aim 1 and previous results to regulate or block
dysfunctional smooth muscle proliferation. It is anticipated that the insights gained from this investigation will
ultimately lead to new therapies that will ameliorate or reverse the hyperplastic smooth muscle pathology of the
disease.
The PI’s long term career goal is to become an independent investigator working on translational problems in
pulmonary vascular disease. In the short term the PI will gain experience investigating problems involving gene
and protein expression, intracellular cell signaling, animal model work and approaches to control diseases with
targeted inhibitors such as cell permeable peptides. Training will involve the PI immersing in lung biology
research through exploration of new physiological techniques via participation in ongoing animal experiments
in his mentor’s lab, attending animal experiment workshops, participation in Pulmonary Division research
seminars and journal clubs, presentations at large and specialized conferences related to lung biology
research and graduate course work in pathobiology and introduction to clinical care research. Overall, this
proposal will provide the candidate enough training in research aspects of lung bio...

## Key facts

- **NIH application ID:** 9962468
- **Project number:** 5K01HL133796-05
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Jamie Lee Wilson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,000
- **Award type:** 5
- **Project period:** 2016-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962468

## Citation

> US National Institutes of Health, RePORTER application 9962468, Regulation of smooth muscle hyperplastic growth in pulmonary (5K01HL133796-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9962468. Licensed CC0.

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