Joel S Greenberger
University of Pittsburgh, PA·Medicine & Clinical Research
High doses of radiation damage the rapidly dividing cells that renew the lining of the intestine, leading to a condition known as the acute gastrointestinal syndrome. Treating it is difficult because radiation also injures the small blood vessels of the gut, so drugs given by injection do not reach the intestinal crypts, the tiny pockets in the gut lining where new cells are made.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Pharmacology
- Topics
radiation mitigation
acute gastrointestinal syndrome
interleukin-22
- Grants
- 1 known grant, through Nov 2027
What they work on
- Test whether the engineered probiotic LR-IL-22 restores gene transcription suppressed by irradiation in Lgr5+GFP+ intestinal crypt stem cells, the fluorescently labeled cells that regenerate the gut lining.
- Test whether oral gavage of a second probiotic, R2Ic, which activates the aryl hydrocarbon receptor (AhR), boosts the intestine's own IL-22 production and adds to the protection given by LR-IL-22.
- Engineer a version of LR-IL-22 with primed rather than constant IL-22 release, to improve therapeutic efficacy while providing biological and environmental containment of the live bacterium.
- Determine whether LR-IL-22 preserves the regenerative capacity of intestinal crypts and reduces acute gastrointestinal injury after total body or partial body irradiation in support of translation to the national stockpile.
More about the research
This project develops an alternative: a probiotic bacterium, taken by mouth, that manufactures a healing protein directly where it is needed.
Why it matters
People exposed to large radiation doses, whether through accidents or during cancer radiotherapy, can suffer severe damage to the intestinal lining with few effective treatments, since injected drugs reach the damaged gut poorly. An orally delivered probiotic that supplies IL-22 directly to injured intestinal crypts could offer a mitigator that works after exposure, and the work also addresses the safety and containment needed before an engineered live bacterium could be used in people.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Marlies Meisel
University of Pittsburgh, PA·Microbiology & Immunology
Test whether checkpoint-inhibitor-response-associated gut bacteria convert dietary tryptophan into molecules that activate the aryl hydrocarbon receptor (AhR) and strengthen interferon-gamma-producing Tc1 CD8 T cells, in cell culture.
John Mountz
University of Alabama at Birmingham, AL·Microbiology & Immunology
Determine which IL-4-induced tryptophan metabolic signals block TLR7-driven autoantibody-precursor B cells in vivo, comparing wild-type mice with mice lacking the B-cell enzymes IL4i1 and Ido1 or the metabolite sensor AhR.
Collynn Woeller
University of Rochester, NY·Microbiology & Immunology
Define the molecular steps by which the aryl hydrocarbon receptor, a chemical-sensing transcription factor, blocks activation of orbital fibroblasts — the connective-tissue cells behind the eye that turn into fat cells and scar-forming myofibroblasts in thyroid eye disease.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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