Research Expertise & Professional Interests
Platelet activation plays a central role in thrombosis and hemostasis, while these processes are central to vascular health and disease. In the platelet lineage, bone marrow stem cells develop into early committed megakaryocyte progenitors, which undergo a unique cell cycle leading to polyploid cells prior to fragmenting into platelets. Our research focuses on mechanisms that regulate these processes under normal conditions vs. pathology. We proposed a new paradigm for controlling the transcription of genes uniquely expressed in this lineage, by identifying a cluster of non-tissue specific transcription factors that, together, constitute a signature uniquely driving this lineage development, among other cell lineages in the bone marrow. Studies were extended to identifying mechanisms governing polyploidy in megakaryocytes, leading also to better understanding of regulatory processes that cause polyploidy in other cells, such as aging vascular smooth muscle cells. Past projects involved molecular characterization of platelet and vascular adenosine receptors, and exploration of their roles in such cellular function. Importantly, knowledge gained by studying basic regulatory processes in healthy megakaryocytes and platelets aids our investigation of bone marrow pathologies, such as myeloproliferative neoplasms (MPNs). The systems used include primary bone marrow cultures, as well as transgenic and knock out mouse models.