The Wisconsin Surgical Laboratory in Metabolism (WiSLiM), run by Dave Harris, MD, an Assistant Professor in the Division of Minimally Invasive Surgery, conducts research on how bariatric surgery affects metabolism and aging, with the goal of developing and testing novel and translatable therapies that can reduce the burden of metabolic diseases, ultimately improving both organ function and healthspan. With the support of two new campus-based research awards, he and his team will be advancing this mission.
WiSLiM will be engaging in the following projects over the next 1-2 years:
- With a one-year, $67,000 Fall Research Competition award from the Office of the Vice Chancellor for Research, they will be studying the effects of incretin hormones on colon health and the risk of colon cancer. Incretin hormones are released by the gut after a meal, stimulating the production of insulin. Two key incretin hormones, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1), have garnered increasing interest as they are the hormones targeted by new anti-obesity medications like semaglutide (Wegovy) and tirzepatide (Zepbound). The use of these medications has been associated with a reduced risk of several types of cancer, including colon cancer; however, the mechanisms by which incretin hormones impact the colon are unknown. In collaboration with Dr. Richard Halberg (Oncology) and Dr. Sam Gellman (Chemistry), the team will be evaluating how the chemistry of incretin hormones affects the cellular biology of the colon and the subsequent risk of colon cancer.
- Harris is also interested in weight loss plateaus that often follow bariatric surgery. Because these plateaus commonly leave many patients with remaining obesity, he and his team are investigating how to move patients past a plateau to continued weight loss. In prior studies they have conducted with mice, the WiSLiM team found that a diet that restricts protein intake – a notion that contradicts the historical dietary approach to weight loss – actually increases energy expenditure and improves glucose sensitivity, leading to improved weight loss. With a two-year, $150,000 New Investigator Program award from the Wisconsin Partnership Program, Harris will collaborate with Dr. Dawn Davis (Endocrinology) and Dr. Dudley Lamming (Endocrinology) to determine the mechanisms that cause this. He also plans to study whether a protein-restricted diet similarly impacts larger animal models of obesity (namely, the Wisconsin Mini Swine™), which is an important step before studies can be done in humans.
“We are grateful for both of these awards, the results of which will set the foundation for future grant applications to the NIH or other agencies, allowing us to generate novel findings that could help us tackle the obesity epidemic in the U.S. and the resulting burden of chronic diseases associated with obesity, including type 2 diabetes and certain cancers,” said Harris.