Dean Sheppard
University of California-San Francisco, CA·Medicine & Clinical Research
Pulmonary fibrosis is a disease in which the lungs fill with stiff scar tissue, making breathing steadily harder. The cells that lay down this scar are fibroblasts, connective-tissue cells that normally support the lung's tiny air sacs (alveoli).
- Fields
Medicine & Clinical Research
Biology
Physiology
- Topics
pulmonary fibrosis
lung fibrosis
fibroblasts
- Grants
- 1 known grant, through Jun 2028
What they work on
- 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.
- Test whether NF-κB signaling, a master switch for inflammatory genes, drives inflammatory fibroblasts in fibrotic and non-fibrotic injury, and how the upstream triggers and induced genes differ between models.
- Delete inflammatory fibroblasts in mice using an SAA3-based genetic line, or block their response to inflammatory signals, to determine whether they are needed for lung fibrosis.
- Delete the TGF-β receptor TGFβR2 or the mechanical sensor Piezo2 from inflammatory fibroblasts to test whether TGF-β signaling and lung stiffness convert them into scar-forming fibrotic fibroblasts.
- Examine normal and fibrotic human lung tissue with Xenium single-cell spatial transcriptomics, immunohistochemistry and multi-color in situ hybridization to test whether the mouse findings hold in patients.
More about the research
After lung injury, these normal alveolar fibroblasts can shift into several different states. This project asks how one of those states, called inflammatory fibroblasts because they respond to immune signaling molecules, arises, what it does, and whether it goes on to become the scar-forming fibroblasts that drive fibrosis.
Why it matters
Pulmonary fibrosis progressively scars the lungs, and patients have few treatment options. Identifying the signals that create inflammatory fibroblasts and push them toward scar formation, such as NF-κB, TGF-β or the stretch sensor Piezo2, could point to new drug targets. Such drugs might interrupt fibrosis before scar tissue builds up. The human tissue studies test whether findings in mice apply to patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Igor Shmarakov
Rutgers University-New Brunswick, NJ·Biochemistry
Determine how endothelial cells, lipofibroblasts and type 2 alveolar epithelial cells take up retinoids from circulating lipoproteins and share them with one another. The approach uses tracer-labeled retinoids, mice lacking Lpl, Cd36 or Lrp1 in specific cells, cultured cells and lipidomics.
Margaret Thomas Freeberg
Virginia Commonwealth University, VA·Physiology·Early-career
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.
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.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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