The Role of CCM Proteins in Intestinal Inflammation
Abstract
Inflammatory bowel disease is a disease of the intestines. Patients with this disease have stomach cramps, intestinal bleeding, and diarrhea. Currently, there is no cure for this disease, and patients have to take drugs all their lives for treatment. In addition, dietary and lifestyle adjustments are often needed. Furthermore, a significant fraction of patients develop this disease as kids or young adults, which can significantly affect physical and mental development. However, we still don’t know why people develop this disease, and treatment options remain limited. Cerebral cavernous malformation is a disease of the brain. Patients have abnormal blood vessels in their brains, which form benign tumors, and these abnormal structures can bleed to cause severe headaches and seizures. Treatment of this disease involves brain or spinal cord surgery, and these procedures can be dangerous. Although inflammatory bowel disease and cerebral cavernous malformation are seemingly unrelated, one can draw some similarities: both of them involve hollow tubular organs, and they both are associated with inflammation. Our preliminary studies show some of the cerebral cavernous malformation patients are more likely to have inflammatory bowel disease, and expression of genes that cause cerebral cavernous malformation are decreased in the gut of inflammatory bowel disease patients. Thus, we propose to understand how the genes involved in cerebral cavernous malformation affect inflammatory bowel disease. We aim to use mouse models to understand how cerebral cavernous malformation genes cause changes in the gut and affect development of inflammatory bowel disease. We will also study samples donated by cerebral cavernous malformation patients to understand how changes of cerebral cavernous malformation genes affect gut function. These studies touch on Fiscal Year 2017 Peer Reviewed Medical Research Program topic areas inflammatory bowel disease and vascular malformation. In this proposal, we are studying the functions of cells lining the inner surface of the intestines and immune cells, the same cells that participate in development of diarrhea. Thus, our study also touches the topic area of diarrheal disease. Our studies will benefit both inflammatory bowel disease and vascular malformation populations by determining why cerebral cavernous malformation patients are more likely to have inflammatory bowel disease and how cerebral cavernous malformation related genes affect inflammatory bowel disease. The proposed work will form a base for more detailed mechanistic studies in the future, which will allow identification of novel targets for therapy of inflammatory bowel disease with high efficiency and fewer side effects. Our work will contribute to our understanding of gut function in health and other diseases, and thus will promote general gut health in humans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810501
Entities
People
- Le Shen
Organizations
- United States Army
- University of Chicago