This application for an Administrative Supplement to the ?Research Training in Rheumatology? T32 Training program grant (AR007534: PI- V. Michael Holers) is submitted in response to NOT-OD-19-087, Notice of Availability of Administrative Supplements for the INCLUDE Project. The purpose of this supplement is to support the professional development of a promising Pediatric Rheumatology trainee, Dr. Jessica Bloom, in research to advance medical knowledge of autoimmunity in individuals with Down Syndrome (DS). This T32 program is based at the University of Colorado Anschutz Medical Campus, which is home to one of the only academic centers fully devoted to DS research - the Linda Crnic Institute for Down Syndrome (Crnic Institute), a premiere center for medical care for children with DS - the Anna and John J. Sie Center for Down Syndrome at Children's Hospital Colorado, and a thriving ecosystem of basic and clinical investigators studying DS. Specifically, this supplement will support investigation to improve the health and well-being of individuals with DS who are affected by idiopathic pulmonary hemorrhage (IPH) and other acute and chronic hemorrhagic lung disorders. Understanding the spectrum of disease among individuals with DS will address unmet health needs and inform the medical community as to the basis for the unique combination of risk and resiliencies of Down Syndrome patients, as well as improve the health of all individuals. Dr. Jessica Bloom has been accepted for a Subspecialists Clinical Outcomes Research (SCORE) Fellowship in the Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS) program at Children's Hospital Colorado. This exceptionally rigorous 2-year program is designed to train investigators in research methodologies and prepare them for academic careers in T4 translational research. Dr. Bloom will use this supplement within this program to test the hypotheses that chronic hyperactivation of IFN signaling promotes development of IPH in DS patients and that consensus-based approaches to diagnosis and treatment can improve timely identification and reduce morbidity and mortality.
The Specific Aims of this proposal are 1) to characterize the clinical spectrum and identify molecular correlates of autoimmunity in DS patients with idiopathic pulmonary hemorrhage and other acute and chronic hemorrhagic lung disorders; and 2) develop consensus based clinical care guidelines for the evaluation, management and monitoring of acute and chronic pulmonary hemorrhage in DS and non-DS patients at Children's Hospital Colorado. The ultimate goals of these studies are to determine if IPH in individuals with DS is clinically and mechanistically similar to IPH in non-DS patients and to assess the impact of specific treatment protocols on patient outcomes and promote the development of local and national collaborative studies. This proposal represents a unique opportunity to bring programs and faculty at UCD together around investigation and management of autoimmunity in people with DS and could lead to novel therapeutic strategies and future clinical trials in this vulnerable population.
Trisomy 21 is the most common human chromosomal disorder, occurring in ~1/700 live births, and results in the condition known as Down Syndrome (DS). Individuals with DS are at increased risk for a variety of autoimmune diseases including disorders casing bleeding in the lungs. The research proposed in this application will improve the identification and management of autoimmune lung disease among DS patients, thereby addressing an unmet health need, informing the medical community as to the basis for these disorders, and improving the health care of all individuals.
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