Rheumatic and autoimmune diseases remain poorly understood, are difficult to manage and treat, and often result in significant morbidity and mortality. This status quo can only be changed by focusing on research efforts that build upon and advance the knowledge that has been generated, re-evaluating current dogmas, and taking advantage of an interdisciplinary collaborative approach to effectively understand these complex multi-system diseases. Unparalleled scientific expansion in genomics, epigenomics, and systems biology has fundamentally enhanced our understanding of human biology, and generated a wealth of data and a unique opportunity to comprehensively investigate the mechanisms underlying human autoimmune diseases. Further, advances in clinical sciences have created outstanding research opportunities to improve patient outcomes. The goal of this Training Grant is to prepare the next generation of researchers to become independent investigators, and lead future efforts to improve care of patients affected by rheumatic and autoimmune diseases. This will be accomplished by selecting the most promising postdoctoral trainee candidates, and providing them with the knowledge and skills for a proposed training period of at least 2 years to prepare them for independence. Our Training Program will include 4 physician-scientists or scientists each year and will prepare them through a carefully designed individualized didactic experience, with structured mentoring focused on both scientific and career growth. In addition, our program will prepare trainees for independence through training in scientific writing, grantsmanship, and leadership skills. This Training Program will be directed by Dr. Amr Sawalha, with Drs. David Fox and Dinesh Khanna as Associate Directors. Together, this Training Grant leadership, supported by an external advisory committee which includes 4 scientific leaders with extensive productivity and mentoring experience, provides a complementary set of expertise to ensure a successful mentoring program focused on basic, translational, and clinical research. The Training Program fosters interdisciplinary research, which is evident by a roster of experienced Program Faculty mentors spanning 15 different units. It is supported by a rich and diverse scientific environment to study autoimmunity at the University of Michigan, including two NIH-funded Autoimmunity Centers of Excellence (ACE) programs ? a Basic ACE and a Clinical ACE ? attesting to our strength in both basic and clinical research. Our Training Program will focus on six major scientific themes: genomics, epigenomics, and bioinformatics; systemic lupus erythematosus; inflammatory arthritis; systemic sclerosis; fibromyalgia and chronic pain; and health care policy and outcome research. There is a significant need for researchers in rheumatic and autoimmune diseases, and a pressing need for making sure that future independent researchers are well trained and equipped to lead the effort to understand the complexity of these diseases, identify novel therapeutic options, and improve patient outcomes. Indeed, our proposed Training Program comprehensively addresses these needs.

Public Health Relevance

Rheumatic autoimmune diseases are associated with significant mortality and morbidity, and remain poorly understood resulting in a lack of effective and safe treatments. There is a challenging shortage of trained researchers to tackle the complexity of these diseases. The goal of this application is to provide comprehensive training for future independent researchers who will lead the efforts to better understand the mechanisms underlying human rheumatic autoimmune diseases, and improve patient care and outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Institutional National Research Service Award (T32)
Project #
5T32AR007080-41
Application #
9965817
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Mancini, Marie
Project Start
1976-07-01
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
41
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Fu, Jiaqi; Nogueira, Sarah V; Drongelen, Vincent van et al. (2018) Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis. Proc Natl Acad Sci U S A 115:4755-4760
Nagaraja, Vivek; Mara, Constance; Khanna, Puja P et al. (2018) Establishing clinical severity for PROMISĀ® measures in adult patients with rheumatic diseases. Qual Life Res 27:755-764
Tsou, Pei-Suen; Coit, Patrick; Kilian, Nathan C et al. (2018) EZH2 Modulates the DNA Methylome and Controls T Cell Adhesion Through Junctional Adhesion Molecule A in Lupus Patients. Arthritis Rheumatol 70:98-108
Ray, Donna; Strickland, Faith M; Richardson, Bruce C (2018) Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells. Clin Immunol 196:97-102
Sarkar, Mrinal K; Hile, Grace A; Tsoi, Lam C et al. (2018) Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Ann Rheum Dis 77:1653-1664
Homer, Kate LaRiviere; Warren, Jeffrey; Karayev, Dmitry et al. (2018) Performance of Anti-Topoisomerase I Antibody Testing by Multiple-Bead, Enzyme-Linked Immunosorbent Assay and Immunodiffusion in a University Setting. J Clin Rheumatol :
McCoy, Sara S; Reed, Tamra J; Berthier, Celine C et al. (2017) Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta. Rheumatology (Oxford) 56:1970-1981
Namas, Rajaie; Beydoun, Nassar; Meysami, Alireza (2017) Breast calcinosis in a patient with Dermatomyositis. Eur J Rheumatol 4:175-176
Hutchings, Kim M; Lisabeth, Erika M; Rajeswaran, Walajapet et al. (2017) Pharmacokinetic optimitzation of CCG-203971: Novel inhibitors of the Rho/MRTF/SRF transcriptional pathway as potential antifibrotic therapeutics for systemic scleroderma. Bioorg Med Chem Lett 27:1744-1749
Mor-Vaknin, Nirit; Saha, Anjan; Legendre, Maureen et al. (2017) DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis. Nat Commun 8:14252

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