Wael Jarjour, MD

My specialty interests include rheumatoid arthritis, vasculitis, Lupus, connective tissue diseases and osteoarthritis with research focused on autoimmunity.

Research interests

• Rheumatoid Arthritis
• Vasculitis
• Lupus
• Connective Tissue Diseases
• Osteoarthritis

Our Lab's Research

Systemic Lupus Erythematosus (SLE)

Therapeutic Targeting using neutrophils and microvesicles in SLE

The Jarjour lab in collaboration with the Lee laboratory is testing novel biochip to transform neutrophils into microscopic vehicles that deliver therapeutic agents to the site of inflammation throughout the body. The study examines the Transfection of Nucleic acids such as microRNA (miRNA) to target inflammatory pathways in lupus nephritis. We recently reported that the use of an anti-MiRNA cocktail (miR-21, mir-29a, and miR-29b) significantly reduced proinflammatory cytokines and histopathological infiltrates in a chimeric model pf SLE. (Inhibition of miRNA)

Myocarditis is detected in NZM2410 mice independent of glomerulonephritis

Our lab has described for the first time myocarditis in a lupus mouse model (NZM2410). We established echocardiography and cMRI with T2 mapping as a method to determine lupus-mediated disease progression in these mice. Disease manifestation by histology was observed prior to kidney disease. Finally, this is the first study to successfully capture cMRI with quantitative T2 imaging in a mouse model. (Pathological manifestation)

Gut Dysbiosis is Associated with Acceleration of Lupus Nephritis

The gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. We explored the effects of Segmented Filamentous Bacteria (SFB) on the lupus disease manifestation in NZM2410. SFB colonization was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition, and interstitial inflammation. This study has significant implications for human disease. (Gut dysbiosis)

HMGB-1 High Molecular Weight Complexes in SLE

The Jarjour lab has discovered that proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and forms high-molecular-weight complexes with autoantigens. Ongoing work is investigating the composition as well as the formation of this form of HMGB1 in SLE and their contribution to lupus pathogenesis. (HMGB-1 High Molecular Weight Complexes in SLE)

Myositis

Another area of active investigation in the lab concentrates on weakened muscle conditions known as inflammatory myopathies. This group of autoimmune diseases is marked by chronic inflammation of muscle tissue. These inflammatory myopathies are part of a heterogeneous group of diseases with diverse etiologies and clinical manifestations. We have demonstrated the role of Tregs in the development of muscle tissue inflammation through the use and development of novel animal models of these diseases (Large functional repertoire). Moreover, our laboratory has developed a myositis mouse model that combines synaptotagmin VII null with FoxP3 mutations, resulting in a mouse with impaired membrane resealing and regulatory T-cell deficiency. This mouse displays robust inflammatory myositis that recapitulate, in part, the human disease (Aberrant Muscle Antigen). Working in collaboration with the Weisleder Laboratory the group has identified antibodies to TRIM72 in patients in myositis patients that compromises cell membrane resealing. This observation lays the ground work for testing if improving membrane resealing could dampen the immune response to muscle proteins in myositis. (Autoantibodies targeting TRIM72).

Rheumatoid Arthritis (RA)

The Jarjour lab in collaboration with Das and Ostrowski labs has been studying various regulators of the inflammatory response in RA (Enhancer variants reveal and Myeloid Krüppel). Moreover, the Jarjour lab (in collaboration with Washington University Roberson lab) is exploring other pathways that can be targeted therapeutically through RNAseq of microRNA, in exosomes isolated from plasma and synovial fluid of patients with RA. Ongoing research focuses on the development of new therapeutic strategies using mesenchymal stem cells (The therapeutic effects). We are studying the role of several genes on the development, maintenance, function of regulatory T cell subpopulation in collage-induced arthritis model.

Sex Bias in Systemic Autoimmune diseases

Our laboratory studies sex bias in systemic autoimmune disorders with focus on Systemic Lupus Erythematosus (SLE). In investigating the role of estrogen receptors and estrogen in SLE and other autoimmune diseases, our team has identified novel targets of estrogen that are significantly up-regulated in SLE patients and play a critical role in regulating inflammation. The long-term goal of this project is to elucidate the role of estrogen and its receptors in the pathogenesis of SLE and identify biomarkers that will define women who are at high risk of developing lupus. Read our ZAS3, TLR8, Estrogen-regulated STAT1, and Inhibition of miRNA papers. Ongoing research is examining the role of a novel estrogen receptor-beta agonist as a therapeutic in lupus.