Nigrovic Lab Research | Overview
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.
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 projects focus 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.
Megakaryocytes as immune cells
Known as the source of platelets, we found that megakaryocytes also serve as immune cells, capable of contributing to the pathogenesis of arthritis and as a source of pro-inflammatory microparticles. We identified a new form of cell-in-cell interaction, termed emperipolesis, whereby neutrophils transit through the cytoplasm of megakaryocytes to transfer membrane and other components to their daughter platelets. Active projects in the lab seek to understand the role of megakaryocytes in immunity, including the mechanism and consequences of emperipolesis for megakaryocytes, platelets, and neutrophils.
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 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 inflammatory arthritis and systemic lupus erythematosus in order to use human genetics to define pathogenic mechanisms and new drug targets.
Dr. Nigrovic also directs the NIAMS-funded Joint Biology Consortium arthritis research infrastructure, a collaborative network dedicated to enhancing the efficiency of existing studies, facilitating innovation in arthritis research, and fostering the next generation of investigators in rheumatology and orthopedics.