Research

The colon is lined by epithelium that lives in constant contact with bacteria and the molecules they make. We build colon organoid models and microfluidic chips in which living bacteria and human epithelium share the same space, so their interactions can be controlled and measured.

Current work asks how bile salts, bacterial enzymes such as bile salt hydrolase, and other microbial metabolites influence bacterial colonization, host signaling and tumor behavior in colorectal cancer organoids.

Fat tissue and the liver signal to each other constantly, and that conversation goes wrong in insulin resistance and fatty liver disease. We culture adipose and liver tissues on chip to study it with human and primary cells under flow.

Our perfused adipose tissue-chips carry preadipocytes differentiated into adipocytes, and adipocytes made insulin resistant. The insulin-resistant adipocytes take up less fatty acid, and rosiglitazone restores uptake. Our liver constructs combine several cell types, stay functional for weeks, and can be made insulin resistant to test strategies that restore insulin response.

Gut bacteria change how drugs are absorbed and metabolized. Our intestine tissue chip grows a tight epithelial monolayer on a collagen membrane instead of the usual Transwell membrane, and we use it to study how gut bacteria modulate cytochrome P450 drug-metabolizing enzymes. Because many gut bacteria need low oxygen, we also built chips with local control of oxygen tension.

We pair these experiments with pharmacokinetic models to understand how bacteria alter drug exposure, for example for tacrolimus and sulfasalazine.

Tissue on a chip changes over days and weeks, and the small volumes make proteins and small molecules hard to measure. We build assays into the chip that read out what cells secrete in real time, without stopping the experiment. Bead-based assays run in line with the culture chamber and measure secreted proteins and metabolites, such as albumin and cholesterol.

Measuring over time turns an organ-on-chip from a single snapshot into a record of how tissue responds to drugs, microbes and nutrients.

Past and collaborative projects include a patient-derived pancreatic cancer-on-a-chip for testing combination drugs, a point-of-care saliva test for periodontitis, analysis of volatile compounds in breath and other samples, and microfabricated columns for gas chromatography.