Margaret Thomas Freeberg
Virginia Commonwealth University, VA·Physiology·Early-career
In idiopathic pulmonary fibrosis, lung tissue fills with excess scar material until the lungs stiffen and can no longer exchange oxygen efficiently; treatment options are few and the disease progresses. Two problems are known to drive it.
- Fields
Physiology
Medicine & Clinical Research
Biomedical Engineering
- Topics
idiopathic pulmonary fibrosis
mechanotransduction
Piezo2
- Grants
- 1 known grant, through Aug 2028
What they work on
- Characterize how the mechanoreceptor Piezo2, a membrane channel that opens under mechanical force, drives metabolic adaptation to increased matrix stiffness, using lung fibroblasts from IPF and non-fibrotic donors.
- Test whether the stiffness-driven metabolic changes in fibroblasts feed back into a pro-fibrotic loop, in which lactate lowers local pH and activates latent TGFβ, a signaling protein that promotes scarring.
- Determine Piezo2's role in fibrosis in vivo using pre-clinical mouse models of pulmonary fibrosis with genetic knockdown and pharmacological inhibition, measuring both fibrosis development and metabolic change.
- Compare the metabolic adaptations identified in cell and mouse models with metabolomics profiles of exhaled breath condensate from IPF patients, to test clinical relevance of the proposed stiffness-metabolism link.
More about the research
One is mechanical: as the lung's extracellular matrix, the scaffold of proteins surrounding cells, becomes stiffer, fibroblasts respond by making still more matrix, a loop that stiffens tissue further. The other is metabolic: IPF lungs carry abnormally high lactate, which lowers local pH and activates latent TGFβ, a signaling protein that pushes cells toward scarring. This project asks whether these two problems are actually one, connected by a cell's ability to feel force.
Why it matters
Idiopathic pulmonary fibrosis is a progressive, often fatal scarring disease with limited therapies. Showing that a stretch-sensing channel links tissue stiffening to disrupted metabolism would identify mechanotransduction as a drug target that hits two disease pathways at once, and testing inhibitors in mouse models provides early evidence of whether that approach can slow fibrosis. Breath-based metabolite measurements could also inform less invasive ways to track the disease in patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yong Huang
University of Virginia, VA·Medicine & Clinical Research
Test whether reducing lung stretch by paralyzing one side of the diaphragm slows fibrosis progression in the outer and lower lung of mice with bleomycin-induced lung injury.
Beiyun Zhou
University of Southern California, CA·Physiology
Identify how loss of the endoplasmic reticulum chaperone GRP78 disturbs mitochondrial energy production and biosynthesis in alveolar epithelial cells, and how this promotes pulmonary fibrosis, using AT2 cell-specific Grp78 knockout mice.
Dean Sheppard
University of California-San Francisco, CA·Medicine & Clinical Research
Compare when inflammatory fibroblasts emerge, how long they persist and what they become in mouse lungs injured by bleomycin, silica or LPS, using Scube2-CreER lineage tracing of alveolar fibroblasts.
The school
Virginia Commonwealth University: 19 labs on PI Pages, $524M a year on research, 438 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.