# Novel Functions of Lung Macrophages and Fibroblasts in Pulmonary Inflammation and Fibrosis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $928,378

## Abstract

The PI of this OIA application is a physician-scientist with an outstanding record of contributions
to science, education and mentoring, clinical practice, and professional leadership and service.
During his 30-year career of NIH-supported research, he has made seminal discoveries that
have advanced our understanding of the normal biology and regulatory processes governing
key lung cells, and the mechanisms by which these processes are dysregulated during
inflammatory and fibrotic diseases. His research program is predominantly focused on two
important cell types – alveolar macrophages (AMs) and lung fibroblasts (Fibs) – with qualifying
R01 awards currently funding studies of each. The current AM project builds upon our prior
report that AMs secrete suppressor of cytokine signaling 3 (SOCS3) within extracellular vesicles
(EVs) that can be internalized by epithelial cells (ECs) to dampen pro-inflammatory JAK-STAT
signaling. Objectives during the award period are to characterize: a) mechanisms by which AM
packaging of SOCS3 within EVs can be modulated; b) the global proteome of AM-derived EVs;
c) effects of AM EVs (and artificial SOCS3-containing liposomes) on allergen-activated
inflammatory signaling in bronchial ECs; and d) effects of vesicular SOCS3 on malignant
transformation of ECs and tumorigenic properties of cancer cells. In a new direction, we will
elucidate the stimuli, signaling, transcriptional, and regulatory mechanisms governing self-
replication of AMs in comparison with other macrophage populations. The current Fib project
builds upon ongoing studies to understand signaling and transcriptional mechanisms involved in
pro-fibrotic properties of Fibs. Objectives during the award period are to characterize: a) the
actions and responsible mechanisms of forkhead box M1 (FOXM1) – a transcription factor best
known as a proto-oncogene but never previously studied in Fibs – in mediating Fib
differentiation to highly pathogenic myoFibs and their apoptosis resistance; b) the interplay of
FOXM1 with other transcription factors; and c) the mechanisms by which prostaglandin E2-cyclic
AMP signaling inhibits FOXM1 and Fib activation, and the role of induction of several molecular
brakes in such inhibition. New directions include characterizing mechanisms by which the drug
bortezomib inhibits Fib activation independent of proteasomal inhibition and elucidating
mechanisms to explain opposing actions of cyclic AMP on proliferation of Fibs vs. ECs. This
OIA will support the PI's program of innovative and translationally relevant research in lung cell
and molecular biology while allowing him to increase his commitment to mentoring and
educational and professional service.

## Key facts

- **NIH application ID:** 9900069
- **Project number:** 5R35HL144979-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MARC L PETERS-GOLDEN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $928,378
- **Award type:** 5
- **Project period:** 2019-03-25 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900069

## Citation

> US National Institutes of Health, RePORTER application 9900069, Novel Functions of Lung Macrophages and Fibroblasts in Pulmonary Inflammation and Fibrosis (5R35HL144979-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900069. Licensed CC0.

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