Christopher Weber
University of Chicago, IL·Physiology
The lining of the intestine has to let water, salts, and nutrients through while keeping gut contents out of the body. Much of that selectivity happens not inside cells but in the narrow seams between them, sealed by structures called tight junctions.
- Fields
Physiology
Medicine & Clinical Research
Biophysics
- Topics
claudin-2
claudin-15
tight junction
- Grants
- 1 known grant, through Jul 2027
What they work on
- Determine which molecular and structural features of claudin-2 and claudin-15 dictate the size and charge selectivity of their pores, using all-atom computer models of the proteins together with first-in-class channel blockers.
- Define the separate and combined contributions of claudin-2 and claudin-15 to normal intestinal physiology by applying existing and newly developed small-molecule blockers of these paracellular sodium channels.
- Test the role of claudin-2 and claudin-15 channels in barrier regulation driven by sodium-coupled nutrient co-transport, the process that pulls glucose and amino acids into intestinal cells alongside sodium.
- Assess how these claudin channels contribute to disease by examining mouse models of colitis and tissue from patients with inflammatory bowel disease, linking channel activity to diarrhea and barrier loss.
More about the research
When those seals go wrong, as happens in inflammatory bowel disease (IBD), celiac disease, and infectious colitis, patients get diarrhea and absorb nutrients poorly. A family of proteins called claudins sets how leaky each seam is and to which ions. Two of them, claudin-2 and claudin-15, specifically control the passage of sodium between gut cells, and changes in their levels are tied to intestinal disease.
Why it matters
Diarrhea and poor nutrient absorption in inflammatory bowel disease, celiac disease, and infectious colitis trace back in part to leaky seams between intestinal cells. Clarifying how claudin-2 and claudin-15 channels move sodium, and showing that small molecules can block them, could explain how nutrients are absorbed and how diarrhea arises during inflammation, and may provide a starting point for drugs that restore the gut barrier.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Fatemeh Khalili-Araghi
University of Illinois Chicago, IL·Biophysics·Early-career
Determine the molecular basis of gating and ion selectivity in claudin pores, the channels between adjacent cells, using atomic-resolution molecular dynamics simulations.
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.
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.
The school
University of Chicago: 39 labs on PI Pages, $681M a year on research, 457 research doctorates a year.
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