The Nigrovic lab studies basic immune mechanisms of arthritis and other rheumatic diseases in adults and children. This work employs both human specimens and murine model systems. Active projects include:

Innate mechanisms of inflammatory synovitis

Our group helped to identify a role for the mast cell in the initiation of murine synovitis. We are interested in the contribution of this lineage to chronic arthritis; in mechanisms that underlie the expansion of these cells in inflamed synovial tissue; and in understanding when mast cells are required and when they are dispensable.

These latter studies have led to new insights in the role of neutrophilsplatelets and megakaryocytes in inflammatory arthritis. Current lab members have projects focusing on the role of Ly6G family members (Ly6G, CD177) in neutrophil migration; on myeloid development; and on megakaryocyte biology.

IgG glycosylation

In murine and human arthritis, IgG can be the primary driver of joint inflammation. The ability of IgG to engage Fc receptors and complement is dependent upon two specific glycans within the Fc region. The distribution of these glycoforms changes in inflammatory arthritis, as well as with age and gender. We are interested in mechanisms underlying these changes and their relevance for immune function and disease pathogenesis. 

T cell-mediated immunological memory in the joint

Clinical observations suggest that patients with arthritis respond better to treatment early rather than late, and that the pattern of joints affected in an individual patient is remarkably stable, even as disease runs a course over many decades. We are interested in changes that occur in T cell phenotype and repertoire that may drive these clinical phenomena.

Genetic insights into arthritis pathogenesis.

We have recently developed several novel molecular tools that help to bridge the gap between genome wide association studies (GWAS) and molecular pathways relevant to disease. We are applying these tools to human rheumatic disease in order to use human genetics to identify pathogenic mechanisms and new drug targets.

Dr. Nigrovic also directs the NIAMS P30-funded Joint Biology Consortium, a multicenter research infrastructure to support arthritis research.

Dr. Nigrovic is a practicing pediatric and adult rheumatologist and directs the Center for Adults with Pediatric Rheumatic Illness (CAPRI) at the Brigham and Women’s Hospital.