Understanding platelets on a cellular level
Versiti Blood Research Institute Investigator Hervé Falet, PhD, is using his expertise in hematology and cell biology to identify gaps in knowledge of the platelet production process.
Platelets are only one component of blood, in addition to red cells, white cells and plasma. Platelets help the blood to clot, and an overabundance or lack of them can be detrimental to an individual’s health. In normal, healthy individuals, platelet counts are somewhere between 150,000-450,000, and gene mutations can cause a platelet count to change within that range. However, platelet counts above or below those two end points can cause serious health issues. Patients with a platelet count below 150,000 experience thrombocytopenia, or a lack of platelets that causes the blood to have difficulty clotting, increasing the risk of bleeding. Patients with a platelet count greater than 450,000 experience thrombocytosis, or an excessive number of platelets, which increases the risk of blood clots, stroke and heart attack, the leading cause of death in the United States.
A key aspect to understanding platelet production and function is studying megakaryocytes. Megakaryocytes are the cells in the body’s bone marrow that produce platelets. These cells form from hematopoietic stem cells, multiply their DNA content through endomitosis, or the replication of chromosomes in the absence of cell division, and expand to form an intracellular maze of membranes, called the demarcation membrane system, from which platelet territories are formed.
Dr. Falet and his peers already know that megakaryocytes can migrate closer to blood vessels, where they release platelets, but no one knows quite how the platelet territories are formed within the cell membranes. Dr. Falet is interested in learning more about the different genes and proteins that play a role in intracellular membrane formation and organization, and platelet production.
Researchers have already identified certain proteins in the body that can affect an individual’s platelets, such as dynamin 2 (DNM2), mutations of which cause neuromuscular diseases associated with low platelet counts and acute lymphoblastic leukemia, and PACSIN2, which affects platelet count and size. By better understanding how these genes affect platelet production, investigators like Dr. Falet can work toward improving platelet counts and developing new treatment methods for patients.
About the expert: Hervé Falet, PhD, is an investigator at the Versiti Blood Research Institute and assistant professor in the Department of Cell Biology, Neurobiology and Anatomy at the Medical College of Wisconsin.