Nigrovic Lab 2019

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 arthritis. Related studies have led to new insights in the role of neutrophils, platelets and monocytes in inflammatory disease. Current lab members have projects focusing on the role of Ly6G family members (Ly6G, CD177) in neutrophil migration and function; on neutrophil subtypes in humans and mice; and on myeloid development; and on the monocyte/macrophage product adenosine deaminase 2 (ADA2), deficiency of which can lead to childhood stroke.

MEGAKARYOCYTES AS IMMUNE CELLS

Well known for their role in hemostasis as the source of platelets, we identified megakaryocytes as a cell capable of activating in the immune system as a source of pro-inflammatory microparticles. We identified a new form of cell-in-cell interaction, termed emperipolesis, whereby neutrophils passage through the cytoplasm of megakaryocytes to transfer membrane and other components to their daughter platelets. These observations have led us to consider megakaryocytes as immune cells in their own right. Active projects in the lab pursue this revised understanding of megakaryocytes, including better understanding of mechanism and consequences of emperipolesis and the role of platelets in inflammatory disease.

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 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 inflammatory arthritis and systemic lupus erythematosus 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.