This is a K23 award proposal for Cailin Sibley, M.D., M.H.S., a rheumatologist and Assistant Professor at Oregon Health & Science University. She is a young investigator with an interest in translational medicine who will be conducting studies of gene expression profiling to elucidate the mechanisms responsible for disease in vasculitis and to investigate whether some cases of idiopathic inflammation may be due to similar mechanisms. These data will be used to study whether gene expression profiling can help predict the severity of a patient's disease course and response to treatment. As the computational methods needed to analyze gene expression data are complex and evolving, she will require further coursework leading to a Master of Science degree in Computational Biology in order to properly address her research questions. Her co-mentors are experienced in the fields of immunology, computational biology, and rheumatology and will guide her future studies and career development. Granulomatosis with polyangiitis (GPA) is a systemic a multisystem necrotizing granulomatous vasculitis of small and medium vessels. Disease manifestations range from life threatening pulmonary hemorrhage and rapidly progressive glomerulonephritis to more mild upper airway manifestations. The mechanisms by which inflammation in GPA occurs are poorly understood and gene expression profiling is an ideal method to study this at the tissue level.
In Aim 1, the gene expression profile will be determined for GPA in the blood, nose, sinus, subglottis, lung and kidney.
In Aim 2, it will be determined if a subset of patients with idiopathic inflammation of the upper airways has a gene expression profile similar to GPA.
In Aim 3, exploratory data will be generated to test if results from gene expression profiling can predict clinical and treatment outcomes in GPA. Results from these studies will be used directly in a R01 application to design a definitive, prospective study of gene expression profiling as a method of predicting disease outcomes and a treatment response in GPA.
Inflammation of blood vessels (vasculitis) can have serious consequences including organ damage and even death. Gene expression profiling measures the activity of genes and is a tool that can help understand the abnormal processes in vasculitis. Through this technique, we can uncover new targets for treatment, may be able to determine which patients will develop severe disease manifestations, and may be able to predict which patients will respond to therapies. As this is an evolving area of research, there is a need to tran young investigators in order to properly apply these techniques to clinical practice.
