Proteome-wide assessment of the impact of citrullination on the activityof transcription factors in Th2 cells

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Project Summary Many proteins are modified after they are produced in cells. Such modification can critically influence the function of proteins. One such modification is citrullination, which has been shown to regulate the function of immune cells, including lymphocytes and neutrophils. Abnormal citrullination has been associated with many human diseases, including infection and autoimmune diseases. Thus, manipulating protein citrullination can be beneficial in many clinical settings; however, our knowledge of citrullination is still very limited mainly due to lack of reliable methods for examining the functional impact of citrullination. The objective of this project is to develop a method that can be used to assess the proteome-wide impact of citrullination on the activity of transcriptional regulators in immune cells. A DNA-proteomic platform will be optimized and subsequently used to compare the activity of transcriptional regulators at a proteomic scale between citrullination sufficient and deficient lymphocytes. The approach can be readily modified and applied to other immune cells. Results thus generated very likely will lead to discoveries of novel therapeutic targets of human diseases.