Lupus Omics Cutaneous Kidney Investigative Team (LOCKIT)

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As the pace of discovery in the biology, genetics, and environmental regulation of SLE accelerates, the speed and efficiency of translational application assumes even greater importance. There is now unprecedented opportunity to harness technological advances to de-and reconstruct the enormity of phenotypic and immunologic heterogeneity in this prototypic autoimmune disease. Building on our clinical infrastructure and technical protocols that yielded high-quality tissue, urine and peripheral cells for transcriptomic and proteomic analyses in AMP1, an expanded team of multi-disciplinary investigators together form the Lupus Omics Cutaneous Kidney Investigation Team (LOCKIT) in response to the FOA: Accelerating Medicine Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) Program. Collective team discussions aligned the most significant scientific opportunities with clinical needs to focus on the kidney and skin, each with its own challenging heterogeneity. Understanding the molecular underpins of both very early kidney disease (with comparisons to data on established/relapsed disease generated in AMP1) and treatment inadequacies overall were considered high priority goals in the field, as were differentiating acute from chronic cutaneous disease and monitoring differences in treatment responses in these skin disease subsets. Availability of tissues to other teams will be complementary as biology is compared across diseases. Replicating successes of AMP1, LOCKIT will be led by the co-chairs of AMP1 SLE Clinical Working Group, Jill Buyon, NYU School of Medicine and Michelle Petri, Johns Hopkins University. They are joined by nephrologist Brad Rovin, Ohio State University, and dermatologist Victoria Werth, University of Pennsylvania, each recognized for translational contributions to SLE. To accomplish our directives and assure sufficient representation of underrepresented minorities among patients, included are three high-recruiting AMP1 sites led by Anna Broder, Albert Einstein College of Medicine; Maria Dall’Era, University of California San Francisco; and Jennifer Anolik, University of Rochester (co-chair of AMP1 and PI of RA site, adding B cell expertise). Two new sites, led by Karen Costenbader, Brigham and Women’s Hospital, and Ben Chong, University of Texas, Southwestern, bring expertise in patient outcomes and cutaneous lupus, respectively. All collaborate and publish together with cohorts collectively totaling 5,541 patients consenting to registries, and archived specimens including 98,980 longitudinal blood derivatives, and 3,311 kidney and 715 skin biopsies. To uniformly anchor discoveries, as in AMP1, Jeff Hodgin, University of Michigan will lead a digital imaging repository. LOCKIT is poised to apply state-of-the-art technologies and next generation analytics provided by scientific partnership with AMP AIM Cores to interrogate tissues and biologic fluids from informative populations. Although focusing on the kidney and skin, our cohorts include all SLE manifestations, providing agility to address other organs as AMP AIM evolves. LOCKIT commits to harmonize and optimize all aspects of the data pipeline, from collection to analysis, interpretation and dissemination.