A Role for APC in Goblet Cell Function and the Unfolded Protein Response
Abstract
About the Principal Investigator: I am currently in my third year of graduate school at the University of Kansas in the lab of Dr. Kristi Neufeld. In our lab, we research a protein called Adenomatous Polyposis Coli (APC), whose function is crucial for preventing colon tumors. After finishing my Ph.D. work, I plan to obtain a postdoctoral research position in a lab focusing on cancer prevention and inflammation. As a predoctoral candidate, I believe that this grant will both allow me to contribute to the field of cancer prevention as well as boost my qualifications that will help with my later career. Objective and Research: Roughly a third of people over the age of 50 have one or more colon polyps. Though benign, some of these polyps will become colon cancers if not removed. An estimated 80% of colon polyps and colorectal cancers have mutations in the gene that specifies the APC protein. The Neufeld lab studies the APC protein to determine how it keeps normal colon tissue from becoming cancerous. I have designed the present study to find new functions for APC that may contribute to halting cancer progression. We previously identified a novel drug compound called KU-32 that can increase the amount of APC and decrease the number of tumors in the mouse intestine. Here we will determine if there are functions of the APC protein that to our knowledge have not been discovered. Finding a new function of the APC may change the ways we think about how APC regulates the colon and could also shed more light on how APC prevents cancer. Our research could lead to better treatments of colon cancer by developing ways to replace a critical function that is lost by APC mutation. In addition to this basic biology, we will also use this grant to continue examining the effects the compound KU-32 has on both normal and inflamed mouse tissue. Previously we found that KU-32 protects mice with inflamed colons by lowering intestinal inflammation and ulceration. Gathering more data on how KU-32 affects the colon will be useful in determining if KU-32 can be helpful in treatment of human inflammatory bowel disease. There are two groups of patients that will benefit from our research. The first being patients with colorectal cancer as we hope that by uncovering more functions of APC we may be able to find new treatments that can replace lost APC functions. KU-32 will be further evaluated for its effectiveness in treating inflammation of the colon. We plan to do this by examining what proteins affected by KU-32 have on mice with inflamed colons. Ultimately, we hope that these data from KU-32-treated mice could be used generate treatments for human patients that suffer from conditions like ulcerative colitis, which is a type of inflammatory bowel disease whose symptoms include loose and painful bowel movements that occasionally contain blood. As a benefit, by developing a new treatment for inflamed colons, we would also be helping to reduce the risk of colorectal cancer as inflammation of the colon increases colorectal cancer risk. The intestines are also a delicate environment, so more research will be needed to fully evaluate if KU-32 affects the composition of the bacteria in the colon, production of mucus that lines and protects the intestines, and absorption of nutrients. Approximately 10%-15% of inflammatory bowel disease patients die from colorectal cancer. According to the American Cancer Society, around 50,000 people will die from colorectal cancer in 2015. Currently in the United States, colorectal cancer is the second leading cause of cancer-related deaths in both men and women combined. As colorectal cancer effects such a large population the proposed research will benefit both active Service members as well as their family members.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610115
Entities
People
- Christian Gomez
Organizations
- United States Army
- University of Kansas