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Jason G. Smith PhD

Associate Professor

Email: jgsmith2@uw.edu | Phone: 206.685.6144

We are interested in understanding how genetic changes associated with inflammatory bowel diseases (IBD) like Crohn’s Disease and Ulcerative Colitis alter the function of intestinal epithelial cells.  One of the theories of how IBD occurs is that the cells of the intestine in IBD patients are not as good at keeping bacteria out of the underlying tissue. The bacteria that get past the intestinal cells then start an immune response that can’t be controlled. An important cell type in the intestine that produces factors to maintain a barrier against bacteria is called the Paneth cell.  Some of the changes in genes that make patients susceptible to IBD have been shown in mice to affect the function of Paneth cells; however, in many cases the reason why the genetic change affects Paneth cells is not clear.  Moreover, large studies comparing the genomes of people with IBD to the genomes of healthy people have identified many genes that might play a role in causing IBD.  Some of these genes have been found to be turned on in Paneth cells, but whether or not they are important for Paneth cell function has not been investigated.  Although we are now able to study the genomes of patients and can look for genetic changes associated with risk for IBD, scientists are currently unable to predict the function of a patient’s Paneth cells just by knowing the genetic changes of the patient.  Since knowing whether or not a patient’s Paneth cells function normally and understanding the ways in which they are defective may be important for predicting the severity of disease and designing therapy, our goal is to understand the link between genetic changes and Paneth cell function.  To perform these studies, we use an exciting new technology called “enteroids” that allows us to culture “mini guts” containing Paneth cells in the lab and test their function.  We are testing cultures of mouse Paneth cells and engineered human cells, but the ultimate goal is to grow enteroids directly from patient biopsies, which are a routine part of IBD diagnostic tests.  Ultimately, we believe that these approaches will allow us to take tissue from a patient through a biopsy, perform tests on them in the lab, and then determine from the test results whether the patient has or is likely to develop IBD, which of their genetic changes might be contributing to the severity of the disease, and what therapies might resolve flare-ups and prevent future inflammation.