Project 458613

Thrombopoietin (TPO) is a hormone that regulates platelet generation which are small cells crucial that mediate cessation of bleeding (hemostasis). Prevailing theory posits that liver hepatocytes continuously produce TPO, and levels are fine-tuned by platelet uptake. However, our lab has recently shown that platelet receptor glycoprotein (GP) Iba is indispensable for TPO generation, but the mechanism of this interaction and the respective partner GPIba receptor is not known. Emerging reports have shown that liver resident macrophages are required for clearance of old platelets. Interestingly, my data shows that these liver resident macrophages are required for platelet-mediated and baseline constitutive hepatocyte TPO generation, and future experiments will elucidate the molecular mechanisms of contribution. Understanding the mechanism of TPO regulation in its entirety is crucial for future research pertaining to platelet generation and, therefore, hemostasis. Moreover, treatment for patients suffering from dangerously low platelet count, as seen in leukemia or immune thrombocytopenia, for example, is currently lacking; sustained response is rarely achieved, and there lacks a gold standard efficacious across all patients. My study will allow for clinical investigation of novel therapies providing alternative therapeutic avenues for suffering patients.