This award will afford the candidate an opportunity to acquire the clinical research training, educational tools, scientific techniques and mentorship that will be instrumental for her to succeed as an independent investigator in Pediatric IBD research as well as an important contributor to the field of IBD. The career development plan will include didactic learning through the K30 program, local GCRC training and training in the ethical conduct of research as well as the research activities proposed in the research plan. Environment: With the protected time afforded by the K23 award and the institutional commitment, the candidate will be able to devote 75% of her time to the didactic component (K30 program) and to completing the scientific proposal described below The mentors for this award bring with an expertise critical to the success of the career and research plan. The Director of Common Diseases Genetics at Cedars-Sinai will provide the training and resources to acquire a solid understanding of genetic research and the Director of the Immunobiology Institute at Cedars-Sinai, will provide the opportunities to incorporate newfound knowledge in the field of immunology into the proposed research and will direct the immune work to be done in this project. Additionally the GCRC will provide the resources and facilities that will be necessary to conduct all genetic testing. Research: Childhood-onset Crohn's disease is often described as having an aggressive clinical course such that patients develop disease complications early in the disease course, often necessitating aggressive medical and/or surgical management. This project proposes that there are identifiable risk factors that determine or predict a more aggressive disease course of Crohn's disease in children. The objective is to conduct a prospective longitudinal cohort study to define the natural history of childhood-onset Crohn's disease and to analyze the demographic, genetic, immune and environmental influences on aggressive disease phenotypes and disease progression.
The specific aims of this project are 1) to establish a clinically well characterized patient cohort from the Western Region of North America to study disease progression or natural history of children with new-onset Crohn's disease and 2) To determine if there are identifiable demographic, genetic, immunologic and/or environmental risk factors that influence aggressive disease phenotypes and disease progression in children with new-onset Crohn's disease. A total of 400 patients from the Western Region of North America will be enrolled. Principal procedures will include data collection on clinical and environmental history as well as blood sampling for genotyping and testing immune response. Collected data will be stored in a secured relational pediatric IBD database. Primary outcome measures include frequency and time to occurrence of complicating disease behaviors and the associations between markers of risk and defined patient outcome. Defining the natural history of childhood-onset Crohn's disease and delineating the potential determinants of aggressive disease progression will lead to long term efforts to define the preclinical natural history of the disease, and to develop intervention studies to prevent progression of clinical disease to clinical complications.
|Dubinsky, Marla; Braun, Jonathan (2015) Diagnostic and Prognostic Microbial Biomarkers in Inflammatory Bowel Diseases. Gastroenterology 149:1265-1274.e3|
|Siegel, Corey A; Siegel, Lori S; Hyams, Jeffrey S et al. (2011) Real-time tool to display the predicted disease course and treatment response for children with Crohn's disease. Inflamm Bowel Dis 17:30-8|
|Markowitz, James; Kugathasan, Subra; Dubinsky, Marla et al. (2009) Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology? Inflamm Bowel Dis 15:714-9|
|Dubinsky, Marla C; Kugathasan, Subra; Mei, Ling et al. (2008) Increased immune reactivity predicts aggressive complicating Crohn's disease in children. Clin Gastroenterol Hepatol 6:1105-11|
|Dubinsky, Marla C; Wang, Dai; Picornell, Yoana et al. (2007) IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis 13:511-5|
|Dubinsky, Marla C; Lin, Ying-Chao; Dutridge, Debra et al. (2006) Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression. Am J Gastroenterol 101:360-7|