Harvard Catalyst Profiles

Platelets are essential for preventing bleeding and have additional roles in the immune response and tissue maintenance. Notably, platelets exhibit functional diversity, but the origins of this heterogeneity are not well understood. Our lab recently discovered that emperipolesis – a unique interaction in which neutrophils migrate through megakaryocytes – contributes to this platelet diversity. During emperipolesis, neutrophils enter into the cytoplasm of megakaryocytes, where they transfer material to daughter platelets, enhancing the ability of these "hybrid platelets" to clot. Emperipolesis occurs naturally in healthy mammals, but it increases markedly during inflammation, including in rheumatic disease. Drivers of emperipolesis, including the mechanisms behind this increase, are still unknown. This project aims to identify the factors that drive emperipolesis and explore ways to regulate it, with potential experimental and therapeutic applications. The student researcher will use a flow cytometry-based assay to study factors that regulate emperipolesis in inflammation. This includes co-culturing megakaryocytes and neutrophils, introducing inflammatory agents (such as cytokines) and potential inhibitors, and analyzing cells by flow cytometry. Initial work will be closely supervised, with opportunities for independent research as skills develop. There will also be chances to present findings at lab meetings. If of interest, the student may engage in further research to validate results, such as live-cell and live-animal imaging. This project offers an introduction to lab research in cell biology and a deeper understanding of immune cell interactions in inflammatory diseases. The work is relevant to the fields of immunology, rheumatology, and hematology/oncology, in both children and adults. This work will be conducted in the lab of Peter Nigrovic, MD (HMS '95), chief of the Division of Immunology at Boston Children's Hospital and a med/peds rheumatologist. The lab is located in the Karp Building at One Blackfan Circle, across from Boston Children's Hospital. We look forward to discussing this opportunity with you! peter.nigrovic@childrens.harvard.edu