Research Interest: Dynamics of Intestinal Immune System                                                     

My research interests focus on mucosal immunity and the dynamics of the intestinal immune system in health and disease. Specifically, my laboratory investigates epithelial-immune cell interactions through an intricate cytokine network and how, if dysregulated, these interactions may be involved in the pathogenesis of chronic intestinal inflammation such as that found in inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC).

One of the major contributions our group has made to this area of investigation is that interleukin-18 (IL-18), an important cytokine in both innate immunity as well as Th1 polarization, plays a pivotal role in the pathogenesis of human IBD. We confirmed these findings using animal models and found that IL-18, in fact, possesses differential roles that is dependent on phase of disease. IL-18 appears to have innate, protective effects on epithelial barrier function in an IL-11-dependent manner early during the course of gut inflammation, while later, in chronic phases, IL-18 plays a more pathogenic role by eliciting Th1-type immune responses (i.e. production of IFNg). Many cytokines display such dichotomous functions depending on the temporal and spatial relationship of various mucosal immune cell populations, with each other and with the intestinal epithelium. 

 Our laboratory has also been able to translate what we have learned from various models of IBD back to human studies. For example, based on data indicating that chromosome 9 (location of mouse IL-18 gene) is important in conferring disease in several animal models of IBD, we have recently described that carriage of a single nucleotide polymorphism in the IL-18 promoter region (-648C) correlates with increased IL-18 plasma levels and is significantly associated with human Crohn’s disease.

Finally, we have also begun an exciting new interdisciplinary collaboration between investigators from biomedical engineering, cardiovascular medicine and radiology, to develop a novel, non-invasive technology to detect and evaluate intestinal inflammation, which has the potential to make a significant impact in the field of gastroenterology. Taken together, we hope to further understand potential mechanisms involved in the pathogenesis of chronic inflammatory disorders, and to develop novel diagnostic and therapeutic modalities for the treatment of chronic intestinal inflammation, such as that typically observed in IBD.

Contact Information:                                                        
Voice: (434) 243-6404
Fax: (434) 243-6407                                                                            
PO BOX 800708
Charlottesville, VA 22908-0708                                             
ttp4e@virginia.edu