Clinical Assistant Professor, Medicine - Gastroenterology & Hepatology
Fellowship: UCSF Gastroenterology Fellowship (2019) CA
Board Certification: American Board of Internal Medicine, Gastroenterology (2018)
Board Certification: American Board of Internal Medicine, Internal Medicine (2015)
Residency: Massachusetts General Hospital Internal Medicine Residency (2015) MA
Medical Education: Pritzker School of Medicine University of Chicago Registrar (2012) IL
Current Research and Scholarly Interests
My research involves high throughput anaerobic culture of gut microbes to generate complex defined microbial communities. These synthetic microbiomes have genetic content, metabolic output, and immunologic effect that is comparable to existing native human gut microbiomes. Moreover these synthetic communities allow for precise control of species and abundance and the opportunity for disease-specific research and therapy.
Currently I am designing and investigating the biological effects of various synthetic communities on recurrent C. difficile colitis, inflammatory bowel disease (IBD), and nonalcoholic fatty liver disease (NAFLD). My research entails engraftment of various synthetic communities in germ free mouse models of IBD (IL 10 deficient and DSS) and NAFLD (FDD fibrosis) to identify microbes that are important for disease modification.
Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome.
2023; 186 (13): 2839-2852.e21
The gut microbiome is complex, raising questions about the role of individual strains in the community. Here, we address this question by constructing variants of a complex defined community in which we eliminate strains that occupy the bile acid 7α-dehydroxylation niche. Omitting Clostridium scindens (Cs) and Clostridium hylemonae (Ch) eliminates secondary bile acid production and reshapes the community in a highly specific manner: eight strains change in relative abundance by >100-fold. In single-strain dropout communities, Cs and Ch reach the same relative abundance and dehydroxylate bile acids to a similar extent. However, Clostridium sporogenes increases >1,000-fold in the ΔCs but not ΔCh dropout, reshaping the pool of microbiome-derived phenylalanine metabolites. Thus, strains that are functionally redundant within a niche can have widely varying impacts outside the niche, and a strain swap can ripple through the community in an unpredictable manner, resulting in a large impact on an unrelated community-level phenotype.
View details for DOI 10.1016/j.cell.2023.05.037
View details for PubMedID 37352836
ENGINEERING A COMPLEX SYNTHETIC MICROBIAL COMMUNITY FOR MODULATION OF BILE ACIDS
WILEY. 2022: S176
View details for Web of Science ID 000870796600200
Design, construction, and invivo augmentation of a complex gut microbiome.
Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex, but not both, limiting their utility. Here, we construct and characterize invitro a defined community of 104 bacterial species composed of the most common taxa from the human gut microbiota (hCom1). We then used an iterative experimental process to fill open niches: germ-free mice were colonized with hCom1 and then challenged with a human fecal sample. We identified new species that engrafted following fecal challenge and added them to hCom1, yielding hCom2. In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by either hCom2 or a human fecal community are phenotypically similar, suggesting that this consortium will enable a mechanistic interrogation of species and genes on microbiome-associated phenotypes.
View details for DOI 10.1016/j.cell.2022.08.003
View details for PubMedID 36070752