Grant: Emerging Team Grant: From Genes to Proteins, Cells, Tissues and Patients

Given the recent successes in identifying genetic risk factors for common diseases, there now is a major scientific challenge to translating the discovery of disease genes into better clinicalpractice. It is therefore imperative to develop scientific strategies to address this challenge. Our Emerging Team will endeavor to meet this challenge with its initial focus on a biological pathway that has been implicated in multiple diseases of the immune system. Specifically, we and others have shown that genetic variation in four genes of an important cell signaling for the immune system hormone IL-23 pathway (including the R381Q variant in IL-23 cell surface receptor) is associated with Crohn's disease, ulcerative colitis and psoriasis. Our Team, which includes basic and clinical researchers, has the diverse set of expertise necessary to understand the mechanisms by which the associated genetic variants influence disease susceptibility as well as to design and test potential therapies. Our Team also has the structures and partners in place for the scientific planning, teaching, dissemination of information, and commercialization of findings. We feel that our proposal is of great clinical relevance as (1) this pathway is a current target in clinical trials; (2) we have developed IL23 receptor-specific bioactive peptide antagonists and (3) we are creating novel models for pre-clinical testing. The Team's program could have significant impact on the well-being, health and productivity (currently a loss of $1.064 billion annually) of inflammatory bowel diseases (IBD) patients (approximately 201, 000 cases) and the enormous burden on our healthcare system caused by these diseases ($753 million in 2008).