Igor Shmarakov
Rutgers University-New Brunswick, NJ·Biochemistry
Vitamin A is essential for keeping the lungs healthy, but how lung cells actually obtain and use it is not fully understood. The standard view is that the liver releases stored vitamin A as retinol, which travels through the blood bound to a carrier, retinol-binding protein 4 (RBP4), and cells convert it into all-trans-retinoic acid (ATRA).
- Fields
Biochemistry
Physiology
Medicine & Clinical Research
- Topics
vitamin A
retinoids
retinoic acid
- Grants
- 1 known grant, through Dec 2028
What they work on
- 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.
- Establish how vitamin A stores in lipofibroblast lipid droplets set whether these lung support cells stay quiet or become scar-forming (profibrotic). The approach uses single-cell RNA sequencing and spatial immunohistochemistry of labeled retinoid-containing cells in mice.
- Define how lipofibroblast-derived retinoids drive ATRA signaling through retinoic acid receptors (RARs) in endothelial and alveolar cells. This signaling is tested for its control of blood-vessel barrier integrity and surfactant lipid production, using genetic and drug manipulation of RARs and lipidomics.
- Test the crosstalk between retinoid-storing lipofibroblasts and the cells they support, using human type 2 alveolar epithelial cells and endothelial cells co-cultured with lipofibroblasts. The goal is to pin down the ATRA–RAR mechanisms involved.
More about the research
ATRA is a signaling molecule that turns genes on and off. This project challenges that view. Preliminary data suggest the lung gets most of its vitamin A from lipoproteins, the fat-carrying particles that circulate after a meal, and stores it locally.
Why it matters
The findings could change how vitamin A is thought to protect the lung, and in turn inform strategies such as nutritional interventions aimed at easing lung disease. The project focuses especially on acute lung injury and on scarring-prone (profibrotic) changes in lung support cells. Showing that local lung stores, not blood levels, protect the air-sac barrier may point to new ways to support patients whose lungs are injured.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
D Foster
Johns Hopkins University, MD·Physiology
Identify the enzymes that convert vitamin A to retinoic acid in adult heart muscle cells, starting from DHRS4, using heart muscle cells and engineered heart tissue grown from human stem cells.
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.
Lora Hooper
University of Texas Southwestern Medical Center, TX·Microbiology & Immunology
Determine how complexes of serum amyloid A, a microbiota-induced epithelial protein, with the vitamin A derivative retinol are assembled inside intestinal epithelial cells and secreted from them.
The school
Rutgers University-New Brunswick: 57 labs on PI Pages, $837M a year on research, 713 research doctorates a year.
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