This K24 Mid-Career Investigator Award application is focused on mentoring and advanced training of clinical and translational researchers on the elucidation of pathogenic mechanisms and preventive strategies of accelerated cardiovascular (CV) damage in systemic autoimmune diseases. In addition, the proposal will further develop and expand a strong translational patient-oriented research (POR) program that examines the role of inflammation and autoimmunity on atherosclerotic CV disease (CVD) in systemic autoimmune diseases. As premature CVD represents one of the most important causes of morbidity and mortality in systemic autoimmunity, it is imperative to better understand the mechanisms leading to enhanced vascular damage and to develop evidence-based interventions that can lead to decreased CV risk in these conditions. The mentorship plan for early career investigators includes close integration and involvement with the candidate's research program, individualized goals and development of independent research projects, coursework and implementation of biostatistical consultation and research coordination support for candidate and her trainees. Dr. Kaplan has an established record of independent, peer-reviewed POR grant funding and strong record of publications. She has successfully mentored and supervised junior investigators devoted to careers in academic medicine. She is currently one of the most active mentors in the Division of Rheumatology at the University of Michigan. Current mentees include two Rheumatology junior faculty, two Rheumatology fellows, one Pediatric Rheumatology fellow, 3 M.D. and Ph.D. postdoctoral fellows, and one Immunology graduate student. As such, this proposal is intended to facilitate and expand Dr. Kaplan's translational research in autoimmunity while protecting her time to adequately mentor trainees. The proposed research plan includes: (1) continued research related to identifying putative mechanisms that lead to premature CV damage in SLE, with a focus on type I interferons and aberrant neutrophils and new expansion of studies into the pediatric lupus population;(2) new and ongoing research into the identification of the interplay of aberrant lipoproteins and the innate immune system in the development of CV damage and potentiation of autoimmune responses in SLE and RA;(3) testing novel pharmacologic interventions that can decrease CV risk in SLE and RA. This award will contribute substantially to the candidate's career objectives by relieving her of patient care and administrative duties and providing protected time for adequate mentorship and advanced training activities. Dr. Kaplan's research is currently funded by federal and non-federal agencies. The University of Michigan provides an outstanding environment and resources, including a Training Grant to train rheumatology research scientists, a NIH-funded Michigan Clinical Research Unit, as well as a NIH-funded CTSA.
Patients with systemic autoimmune diseases have a significant increase in atherosclerotic cardiovascular risk, which significantly contributes to morbidity and mortality. This proposal will support the expansion of patient- oriented research in this field which may lead to the identification of novel biomarkers and preventive strategies for this potentially lethal complication.