Calvin Kuo, MD, PhD

Bioengineered Wnt Molecules Stimulate Intestine and Liver Growth

K. Christoper Garcia, PhD

In May, Nature published two back-to-back manuscripts from the groups of Calvin Kuo, MD, PhD, D’Ambrogio Professor of Medicine, and K. Christopher Garcia, PhD, Professor of Molecular and Cellular Physiology and HHMI Investigator. Both studies involved use of a bioengineered Wnt surrogate.

The bioengineered Wnt surrogates used in both studies differ from native Wnt molecules. Native Wnt molecules possess a lipid modification that renders them difficult to purify and severely restricts their circulation in the bloodstream. In contrast, the new bioengineered Wnt surrogates are not lipid modified, affording vastly improved pharmacokinetic properties that could lead to therapeutic uses. 

In Garcia’s study, for which Kuo was second to senior author, the artificial Wnt surrogate was generated and used to stimulate liver regeneration and organoid growth. In Kuo’s study, with Garcia as second to senior author, the bioengineered Wnt was used to investigate stem cell biology and promote intestinal growth in combination with a second hormone, R-spondin. 

The first author of Kuo’s study was Kelley Yan, MD PhD, who was performing her Stanford gastroenterology fellowship at the time the research was performed. Prior to that, Yan had been an Internal Medicine resident in Stanford’s Translational Investigator Pathway. Kuo, who serves as vice chair for Basic and Translational Research, says, “This is a wonderful example of the physician-scientist training afforded by the Stanford Department of Medicine.”

The Kuo Lab explores stem cells as a main focus. Scientists in the Kuo Lab work not only to understand how intestinal stem cells are able to repopulate the entire 25-foot length of the intestine every week but also to determine if these stem cells can be harnessed for treatment of diseases.