Grant: Project Grant

Platelets are tiny cell fragments in blood circulation in charge of the prevention of bleedings. However, in systemic lupus erythematosus (lupus), our studies and that of others demonstrate that platelets can aggravate the disease. They produce molecules that promote inflammation and they can plug blood vessels, a process known as thrombosis. As there is no cure for lupus, we propose to examine whether we can treat this disease by the identification of targetable molecules relevant to platelet biology. Platelets are made by megakaryocytes, a giant cell located in bones and lungs, making them hard to study. Each megakaryocyte can generate up to 5,000 platelets. In this project, we propose to study megakaryocytes in lupus to determine whether there are defects in these cells that promote them to generate dangerous platelets. We will use mouse models that we have generated and will study megakaryocytes in bones, lungs and spleen. We will examine how these cells produce the energy they require for their functions and for their platelet progeny, and will determine whether these pathways are dysregulated in lupus. We will then target these pathways and will examine the effects on disease development. We will also include lupus patients, in which we will monitor molecules relevant to megakaryocytes that we will have identified. Our findings could bring a paradigm shift in how we think of lupus classification and treatment through the implication of a new underappreciated immune cell: the megakaryocyte. New therapies that specifically target platelet/megakarycoyte immune functions could offer relief to patients without making them more vulnerable to bleedings. As megakarycoytes produce billions of platelets each day, we may reveal how to target the pathogenic megakarycoyte progeny, platelets, directly at their source.