How do immune responses of the intestinal lining contribute to inflammatory bowel diseases (IBD)? The goals of this project are to determine how cells of the intestinal epithelium are “hardwired” to respond to immune stimuli and how stable changes to these responses are related to IBD. It is known that multiple inflammatory factors produced by […]
Ulcerative colitis (UC) is characterized by non-resolving pathological inflammation leading to erosion of the colon tissue. Recent studies analyzing gene expression signatures in UC patients highlighted specific colonic fibroblast populations that may contribute to inflammation and disease progression. While these studies emphasize the proinflammatory function of activated intestinal fibroblasts, it is unknown whether subsets of […]
Patients with inflammatory bowel diseases (IBD) can experience many years of inflammation and remission in the gastrointestinal tract. As a result, the intestines can undergo a structural change known as fibrosis, which narrows the inside. This narrowing is a major, and sometimes life-threatening, health issue for patients because it can block the passage of digested […]
Patients with inflammatory bowel diseases (IBD) require timely and efficacious therapeutic intervention. When conventional medications such as corticosteroids or 5-aminosalicylates fail to alleviate the disease, biologics that block a critical inflammatory molecule called tumor-necrosis-factor alpha (TNF_) are commonly used. Several drugs targeting TNF_ are currently used to treat IBD, which include Infliximab, Adalimumab, Etanercept, and […]
Recently there has been increased evidence that patients with Crohn’s disease (CD) commonly have disrupted sleep, and disrupted sleep correlates with the risk of disease flare. The sleep/wake cycle, immune function, and multiple biological processes are orchestrated by the circadian clock. The central circadian clock in the brain entrains these processes to the environment by […]
The intestine exerts the vital function of maximizing nutrient uptake from the diet we ingest, being constantly exposed to external stimulation by food components. Alterations in the timing of food intake and diet composition have been associated with the development of immune-related intestinal dysfunctions, including IBS. However, despite its profound biological and clinical relevance, there […]
Inappropriate and chronic inflammatory responses underly the development of inflammatory bowel diseases (IBD), including both ulcerative colitis and Crohn’s disease. This process is an intertwined, inter-cellular cascade among diverse immune cells and tissue stroma. The interactions between immune and stromal cells not only propagate inflammatory responses but also regulate resolution of inflammation. Yet, we do […]
It is now well recognized that IBD develops as a result of complex gene-environment interactions. Since there is no cure for IBD, treatment has focused on alleviating the symptoms. A better understanding of the fundamental mechanisms that drive the development and progression of IBD would allow for the design of more specific and effective treatments. […]
The microbes that flourish within our guts are central to many aspects of human health. Which microbes are present can dictate susceptibility to a number of acute and chronic diseases, including IBD. This proposal will use a mouse model with a defined and stable set of bacteria to probe how mice interact with specific members […]
Pain is a major component of inflammatory bowel diseases, increasing the suffering of patients and decreasing their quality of life. However, the underlying cellular basis for pain in IBD and the role of pain-mediating neurons in driving gut dysfunction are not well known. Our goal is to characterize the role of neurons that mediate pain […]