B cells play central pathogenic roles in many human autoimmune diseases including Systemic Lupus Erythematosus (SLE). Understanding and effectively treating human autoimmunity will require a deep understanding of the antigenic, cellular and molecular events that contribute to the breakdown of B cell tolerance and the downstream events leading to acute clinical disease through the generation of effector cells and to chronic autoimmunity through the formation, maintenance and reactivation of long-lived autoimmune memory. The Emory Autoimmunity Center of Excellence (ACE) U19 proposes an integrated approach to elucidating these central questions through three highly synergistic projects and the use of state-of-the-art technology. The Principal Project (Dr. Sanz, PI), will elucidate the relative participation of naive and memory cells in the generation of antibody secreting cells expanded during acute lupus flares, the antigenic drives responsible for these expansions and the cellular basis of different types of lupus autoantibodies. The Collaborative Agenda (Dr. Boss, PI), will use transcriptional and epigenetic studies to map the signaling pathways responsible for the cellular events addressed in the Principal Project. In turn, these studies will provide a scientific and technological platform that the Emory ACE U19 will extend to other ACE centers to similarly study other immune cell types and human autoimmune diseases. Finally, the Pilot Project (Dr. Jacob, PI), will dissect the molecular determinants responsible for the survival of human long-lived plasma cells. The scientific mission of the Emory ACE U19 will be supported by a well-integrated Administrative Core led by Dr. Sanz who has served in a similar role for more than 10 years as PI of the Rochester ACE. The Emory ACE will also provide major input into the ACE Steering Committee actively contributing to developing the scientific agenda of the network and to the design and implementation of mechanistic studies both through the U19 Collaborative Agenda and the UMI-supported clinical trials.
The Emory ACE U19 will pursue an integrated approach to the cellular and molecular mechanisms of B cell dysfunction in Human SLE. Through the Collaborative Project, it will enlarge its reach to study other immune cells and autoimmune diseases. The expected results should greatly enhance our ability to diagnose, treat and prevent autoimmune diseases.
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