Warren Alexander-Projects

Warren Alexander-Projects


Molecular regulation of megakaryocyte development

Megakaryocytes are the specialised cells in the bone marrow that produce blood platelets, the small anucleate cells responsible for effective blood clotting. Our laboratory has a long-standing interest in the molecular regulation of megakaryocyte production. Current studies include defining the cellular targets and actions of thrombopoietin (TPO), the major cytokine regulator of megakaryopoiesis, and application of gene expression profiling and genomics tools to discover novel megakaryocyte regulators.

Molecular regulation of haematopoietic stem cells

Haematopoietic stem cells (HSC) coordinate the maintenance the diverse variety of functional blood cells over a lifetime. Accordingly, HSC have the properties of both self-renewal, the capacity to maintain a fully potent stem cell pool, and differentiation, allowing the controlled production of maturing blood cells. Defining the molecular regulators of HSC has proven elusive, due to the rarity of these cells and their inability to be maintained in vitro. Our current studies include dissection of stem cell regulation via genetic screens, and detailed analysis of the roles of important stem cell regulators.

Genetic dissection of leukaemia

Leukaemias, the cancers of the blood, arise via the accumulation of genetic lesions that subvert normal cellular regulation and result in unrestrained proliferation. Understanding the genetic landscape that defines leukemia – the variation in disease causing lesions and the interactions between accumulated mutations – will provide powerful insights into how disease arises and progresses, and create new opportunities for improved leukemia diagnosis and treatment. Our current studies include application of genomics and genetics tools to define genetic lesions driving specific leukaemias, with particular focus on disease progression, the evolution to more malignant disease, and the genetic changes influencing response to therapy.