Research

We believe that generating fundamental scientific knowledge is the most promising path to discover new therapeutics and benefit humanity. Areas of research in our lab include:

Discovery of chemosensors in the gut lumen. Our long-term goals are to define general principles of molecular recognition in the gut and to elucidate mechanisms by which microbial metabolites impact human physiology and health. Using a combination of germ-free mice, bacterial strains isolated from human fecal samples, and massively parallel reporter assays in cell lines and human enteroids, we are working to “deorphanize” receptors in the gut and decode the logic for ligand detection and discrimination in the intestines. We collaborate extensively with Dr. Mike White’s laboratory (Washington University in St. Louis) to achieve these goals.

Molecular mechanisms and ecological effects of gut microbial enzymes. We hypothesize that dynamic regulation of signaling molecules, including homoserine lactones, drives microbial interactions within the gut ecosystem. What are the causal links between specific gut bacterial strains, the small molecules that mediate interbacterial communication, and gut microbial ecology? What mechanisms underlie these spatial interactions? We work closely with the laboratories of Dr. Neel Shah (Columbia University) and Dr. Pete Greenberg (UW Microbiology) to investigate these questions.

Developing microbiota-directed nutritional interventions to rectify gastrointestinal (GI) dysfunction in people with cystic fibrosis (PwCF). PwCF experience persistent GI symptoms including abdominal pain, bowel obstruction, impaired gut transit times, and gut inflammation. Our previous work developing microbiota-directed foods that demonstrated treatment efficacy in malnourished children suggests this approach may be applicable to PwCF. Our objective is to develop nutritional interventions that combat GI dysfunction and associated malnutrition in PwCF by restoring a healthy configuration of the microbiota. We are partnering with the research group of Dr. Ben Ross (Dartmouth’s Geisel School of Medicine) and are immensely grateful for NIDDK P30 pilot award funding to pursue this goal.