Joseph Lee
University of Colorado Denver/Anschutz Medical Campus, CO·Microbiology & Immunology·Early-career
The gut lining is a single layer of cells that must let nutrients in while keeping trillions of bacteria out. It also has to repair itself quickly when damaged.
- Fields
Microbiology & Immunology
Physiology
Biochemistry
- Topics
gut microbiota
microbiome
purines
- Grants
- 1 known grant, through Jul 2027
What they work on
- Test whether the microbial purine hypoxanthine shapes the energy metabolism of gut lining cells by turning on TIGAR, a protein that reroutes sugar metabolism, and AMPK, a master energy sensor.
- Determine how gut bacteria-derived hypoxanthine affects barrier function and wound healing, using purine depletion and recolonization with a mutant E. coli engineered to produce extra hypoxanthine.
- Assess whether the hypoxanthine-producing engineered E. coli could act as a next-generation probiotic that improves gut healing in disease models, using colonic enteroid cultures and tissue analysis.
More about the research
When this barrier fails, the result can be inflammatory bowel disease (IBD), a chronic condition affecting millions of people. Gut bacteria help the lining by supplying molecules it uses as fuel. The team has shown that hypoxanthine, a purine (a building block related to DNA bases) made by gut microbes, is something the gut lining depends on for energy, barrier function and wound healing. This project asks how that microbial molecule reshapes the energy use of gut cells.
Why it matters
Loss of the gut barrier is a hallmark of inflammatory bowel disease, which affected about 6.8 million people worldwide in 2017 and is becoming more common. If purines made by gut bacteria help the gut lining heal, they could become a new treatment avenue. This work also tests whether a bacterium engineered to make more hypoxanthine could serve as a probiotic to help patients with IBD.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Pawel Kiela
University of Arizona, AZ·Microbiology & Immunology
Determine whether loss of NAD+ or excess PARylation by the enzyme PARP1 is the main driver of experimental colitis, using PARP1 knockout mice and drug inhibition.
Eliseo Castillo
University of New Mexico, NM·Microbiology & Immunology
Determine how varying doses and types of microplastic particles alter intestinal permeability, meaning leakiness of the gut lining, using a zebrafish exposure model.
Jenessa Winston
Ohio State University, OH·Microbiology & Immunology·Early-career
Test whether daily supplementation with the secondary bile acid ursodeoxycholic acid (UDCA) changes susceptibility to and severity of Clostridioides difficile infection in IL10-knockout colitis mice.
The school
University of Colorado Denver/Anschutz Medical Campus: 41 labs on PI Pages, $766M a year on research, 205 research doctorates a year.
More about University of Colorado Denver/Anschutz Medical Campus
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