The Wharton Summer Student Research Program is a paid, 10-week opportunity for rising junior and senior undergraduate students in nutrition to participate in research projects under the direction of faculty members in the Department of Nutrition and nutrition researchers in the greater Cleveland area.
Participating students receive a stipend and are expected to devote 32-40 hours per week to their projects for the full 10 weeks. Wharton Summer Research opportunities will occur from May 30, 2023 until August 4, 2023.
Eligibility and Applications
Current sophomore and junior undergraduate students who have declared a major in Nutrition or Nutritional Biochemistry and Metabolism no later than January 2, 2023 and have not previously participated in the Wharton Program are eligible to apply for a Wharton Summer Student Research project. A Q&A session will be held January 25, 2023 at 11:30 AM in BRB 932. Applicants are encouraged to attend this session to learn more about the available projects.
Applications are due no later than February 6, 2023 at 5:00 p.m.
Applications will be reviewed by late February, and matches will be announced on or before March 8, 2023.
2023 Projects and Mentors
Effect of an anti-inflammatory diet on gut homeostasis in experimental Crohn's disease
The inflammatory bowel disease (IBD) subtype, Crohn’s disease (CD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Although the precise etiology of IBD is not known, evidence suggests that environmental factors, including dietary nutrients, contribute to its pathogenesis. Diet has been shown to have a pro-inflammatory effect in CD, but not much is known about anti-inflammatory diets, such as soy. Gut microbial modulation via diet is considered as one of the most essential strategies for the therapeutic management of CD; however, no specific recommendations exist for CD patients. Moreover, studies in humans show that the person-specific changes elicited by dietary interventions on host immune and metabolic function are likely due to unique microbiota signatures. This proposal will focus on the microbiota-mediated effects of dietary soy supplementation in patients with active CD compared to healthy controls. The central hypothesis of this proposal is that a soy diet induces anti-inflammatory microbiota in CD patients, and that the ‘level of response’ for each individual can be predicted by metabolic and microbiome biomarkers. We will test this hypothesis directly in humans with active CD, and mechanistically focus on the effect of dietary soy on the ‘pro-inflammatory potential’ of gut microbiota in CD patients. Experimentally, we will use our validated human gut microbiota SAMP1/YitFC (hGM-SAMP) mouse model of CD-ileitis to quantify and mechanistically validate the functional effect of human feces on the severity of CD-ileitis after transplantation into GF SAMP. As a main objective, we will determine to what extent a soy-based diet could induce changes in fecal/blood inflammatory biomarkers in patients with active CD. One of the aims is a continuation of our efforts to understand the microbiota-mediated effects of diet on intestinal inflammation. Specifically, we will characterize the effect of dietary soy in humans with active CD and quantify the inflammatory potential of their gut microbiome using a ‘rapid screening’ hGM-SAMP DSS-colitis model. By stratifying inflammatory microbiome/blood markers, we will identify biomarkers that could predict ‘responders’/‘non-responders’ to diet. We expect to generate a list of metabolic and microbiome clinical biomarkers that could be used to monitor response to diet in CD patients.
Effect of anaplerotic propionate on the growth and metabolic profiling of colon cancer cells
Anaplerosis is the process by which intermediates of the citric acid cycle (CAC = Krebs cycle) are replenished. The intermediates carry the acetyl group of acetyl-CoA as it is oxidized in the cycle. The small pools of CAC intermediates are depleted by low-rate leakage from the cell (cataplerosis). So, the cells need a constant supply of anaplerotic substrates. Colon cancer cells in culture are provided with high concentrations of 2 anaplerotic substrates: glucose (25 mM) and glutamine (5 mM). These anaplerotic substrates are needed for cell growth in vitro. In contrast, when growing in the colon, the cancer tissue is in contact with very low concentrations of glucose and glutamine. However, the cancer tissue is in contact with very high concentrations (10-15 mM) of anaplerotic propionate derived from colon fermentations. Plasma concentrations of propionate are minuscule (0.01 mM). The role of colon propionate in the metabolism of colon cancer has not been explored so far. We hypothesized that colon-generated propionate plays a role in the metabolism and growth of colon cancer. Our initial experiments on cultured colon cancer cells shows that addition of 3 mM propionate to the culture medium increases the rate of cell division. We wish to explore the role of propionate on the growth and metabolism of cultured colon cancer cells, using a combination of metabolic, metabolomic and stable isotopic techniques. We will explore the influence of propionate on pathways of intermediary metabolism (including the CAC and anaplerosis) on cultured cancer cells. It is not clear whether, in colon cancer cells, high concentrations of propionate (i) stimulate cell growth via stimulation of anaplerosis, or (ii) inhibit the CAC via coenzyme A trapping, as is the case in livers perfused with propionate (as shown by Kirkland Wilson, a former Nutrition PhD student in Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism). Variations in propionate concentration in the colon could possibly influence the metabolism of colon cancer, especially in malnourished patients.
This pre-clinical project is conducted in collaboration with investigators of the Case Comprehensive Cancer Center (see Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors and Colorectal cancers utilize glutamine as an anaplerotic substrate of the TCA cycle in vivo).
Metabolic consequences of mutations in the Slc22a5 carnitine transporter
The Lund Lab generally studies how gut microbes interact with the intestinal epithelium to promote homeostasis and how these interactions become altered in pathological states like inflammatory bowel disease. Currently, we are focused on understanding how small molecules produced by microbes serve as metabolic precursors and receptor ligands, thereby influencing energy balance and gene expression in epithelial cells. For Summer 2023, we will have an opportunity for an undergraduate student to contribute to both of our research directions. Using stable isotope tracing, we recently demonstrated that the microbiota processes dietary fiber into carbon sources that support fatty acid metabolism in the epithelium. These carbon sources likely include both short-chain and long-chain fatty acids, the latter of which depend on carnitine for their mitochondrial import and subsequent oxidation. Epithelial cells are thought to rely mainly on short-chain fatty acids to fuel their metabolism, but we hypothesize that long-chain fatty acids are also important since mice with a mutation in the Slc22a5 carnitine transporter develop spontaneous inflammation, possibly due to metabolic deficiencies. To investigate the impact of the Slc22a5 mutation on fatty acid metabolism, the student will use mass spectrometry to assess the metabolic health of mutant cell lines and to track the transfer of carbon from fatty acid precursors to downstream intermediates.
Novel activities of vitamin E
Vitamin E (alpha-tocopherol) is an essential dietary antioxidant that is thought to prevent disease by combating oxidative stress. Indeed, vitamin E deficiency causes pathologies that are traditionally considered outcomes of oxidative damage to cells and tissues.
We have recently found that in addition to these established functions of alpha-tocopherol as a food-borne antioxidant, the vitamin regulates the expression of certain genes. Moreover, this regulation has important consequences on the proper functioning of cells and tissues. We are investigating the molecular mechanisms that underlie these activities, and their outcomes on important biological endpoints. Our approach is based cell biology, involving cultured cells, recombinant DNA techniques, and analyses of gene expression and cell signaling.
The Wharton fellow will be trained to understand the relevant current literature, to master relevant laboratory experimentation, data analyses and interpretation, and to communicate the work to others.