Evan Lee

Program: Computational and Systems Biology

Current advisor: Jeffrey I. Gordon, MD

Undergraduate university: University of California-Berkeley, 2018

Enrollment year: 2020

Research summary
Prevotella copri mediates host ponderal growth and dietary glycan cross-feeding to other bacteria

Undernutrition remains a persistent challenge globally and is linked to 45% of deaths of children under the age of 5. Intestinal abundance of Prevotella copri has been associated with increased weight for length Z-score (WLZ) in clinical studies of therapeutic foods for moderate acute malnutrition. We have developed a gnotobiotic mouse model of a defined microbial community consisting of bacterial taxa representing the developmental trajectory of the Bangladeshi microbiota of healthy children. Assembling this community with and without P. copri reveals that P. copri promotes ponderal growth (weight gain) on a background diet supplemented with therapeutic food and leads to increased dietary glycan degradation of arabinans, galactans, and pectin through a diverse set of polysaccharide utilization loci. We additionally observe increased fitness and expression of genes involved in arabinose utilization by bacteria capable of metabolizing it, as well as profoundly different cecal profiles of bile acids, amino acids, short chain fatty acids, and other microbial metabolites with known signaling function. Using a combination of in vitro, in vivo, and computational techniques, I seek to understand how P. copri colonization promotes changes in host metabolic state leading to ponderal growth and how microbial metabolites produced by P. copri and other commensals affect enterocyte and epithelial biology along the length of the gastrointestinal tract.

Graduate publications
Hibberd MC, Webber DM, Rodionov DA, Henrissat S, Chen RY, Zhou C, Lynn HM, Wang Y, Chang HW, Lee EM, Lelwala-Guruge J, Kazanov MD, Arzamasov AA, Leyn SA, Lombard V, Terrapon N, Henrissat B, Castillo JJ, Couture G, Bacalzo NP Jr, Chen Y, Lebrilla CB, Mostafa I, Das S, Mahfuz M, Barratt MJ, Osterman AL, Ahmed T, Gordon JI. 2024 Bioactive glycans in a microbiome-directed food for children with malnutrition. Nature, 625(7993):157-65. PMCID: PMC10764277

Chang HW, Lee EM, Wang Y, Zhou C, Pruss KM, Henrissat S, Chen RY, Kao C, Hibberd MC, Lynn HM, Webber DM, Crane M, Cheng J, Rodionov DA, Arzamasov AA, Castillo JJ, Couture G, Chen Y, Balcazo NP Jr, Lebrilla CB, Terrapon N, Henrissat B, Ilkayeva O, Muehlbauer MJ, Newgard CB, Mostafa I, Das S, Mahfuz M, Osterman AL, Barratt MJ, Ahmed T, Gordon JI. 2024 Prevotella copri and microbiota members mediate the beneficial effects of a therapeutic food for malnutrition. Nat Microbiol, 9(4):922-37. PMCID: PMC10994852

Lee EM, Verma M, Palaniappan N, Pope EM, Lee S, Blacher L, Neerumalla P, An W, Campbell T, Brown C, Hurst S, Marshall B, Hershey T, Nunes V, López de Heredia M, Urano F.. 2023 Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders. Front Genetics, 14():1198171. PMCID: PMC10321297