Simon Schworer, PhD
Assistant Professor, Department of Medicine, University of Chicago
Novel systems to study the metabolic determinants of cancer-associated fibroblast heterogeneity
breakthrough board scholar
Can changes to the metabolic environment of a pancreatic tumor detect whether cancer-associated fibroblasts are cancer-promoting or cancer-suppressing?
Pancreatic cancer is one of the most difficult cancers to treat, in part because of the extensive network of supporting tissue that surrounds the tumor. This network of fibrotic stroma is created by cancer-associated fibroblasts (CAFs,) which are non-malignant cells similar to the fibroblasts that help to regenerate tissue after an injury. Unfortunately, in cancer these cells have been shown support the growth of tumor cells and to impede cancer therapy.
Dr. Schwörer’s work focuses on the recent discovery that there are functional subtypes within the populations of cancer-associated fibroblasts inside the pancreatic tumor environment; some CAFs suppress tumor growth rather than supporting it. How this heterogeneity develops is not yet understood; it is dependent on the tumor environment which means that traditional cell cultures are not a useful model. Dr. Schwörer has already shown an association between the spatial organization of the CAF sub-types in pancreatic tumors and the specific metabolic environments induced by pancreatic cancer cells. By altering the metabolic environment, he has found he can direct functional diversity in CAFs. With his Young Investigator Award project, Dr. Schwörer will now develop a novel culture system that will closely recapitulate the metabolic tumor environment. By combining this model with a genetic toolset he has already designed, he hopes to discover the metabolic dependencies that determine whether a cancer-associated fibroblast will be tumor supporting or tumor restraining. Finally, Dr. Schwörer will also develop a mouse model to assess the role of these metabolic dependencies in CAFs in pancreatic tumors. If Dr. Schwörer is able to identify how metabolic conditions affect CAF functionality in pancreatic cancer, he will have identified an innovative target for new pancreatic cancer therapies, one which may prove useful in other cancers as well.