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Research Projects | Overview

At the Megakaryocytes to Platelets Research Group at Boston Children’s Hospital, we research how megakaryocytes make blood platelets, and the role(s) that these platelets play in different disease states. The group was founded by our two principal investigators, Joseph Italiano Jr. and Kellie Machlus.

 

Joseph Italiano and Kellie Machlus in the lab

The Italiano Lab

Joseph Italiano and lab members standing outside buildingWelcome to the Italiano Lab. Our research uses cell and molecular biology methods to address problems in megakaryocyte and platelet biology. The lab’s research focuses primarily on how blood platelets, which function as the Band-Aids of the bloodstream, are produced from megakaryocyte precursor cells. Specifically, the lab uses mouse megakaryocyte and human culture systems to study platelet production in vitro. Our primary methods include fluorescence microscopy, live cell imaging, molecular biology, biochemistry, electron microscopy, bioengineering, and knockout mice. Where possible, we attempt to study the dynamics of proteins in living megakaryocytes or reconstitute cellular process with cell extracts. Our lab has demonstrated that platelet formation follows a defined set of morphogenetic shape changes driven by forces derived from both microtubules and actin filaments.

Current focuses include understanding the molecular signals that trigger platelet production, using biologically inspired engineering to establish how the bone marrow microenvironment influences platelet production, understanding how the cytoskeleton powers platelet production. We also have a major interest in understanding the non-hemostatic roles of platelets in health and disease. This includes establishing how platelets regulate new blood vessel growth, immunity, cancer, wound healing, and potentially aging.

The Machlus Lab

Kellie Machlus and lab members standing outside buildingThe Machlus Lab is focused on identifying molecular mechanisms of megakaryocyte development that lead to enhanced platelet production, with specific emphasis on how inflammation affects megakaryocyte function. In many inflammatory conditions, platelet counts rise acutely, resulting in thrombocytosis; what initiates this platelet up-regulation is not well understood. The Machlus lab uses inflammation as a model of exacerbated, TPO-independent hematopoiesis that results in differences in platelet quality and quantity in order to:

 

  1. Gain a better understanding of the basic biology of megakaryocyte maturation and platelet production.
  2. Identify TPO independent pathways of megakaryocyte maturation.
  3. Determine ways to reduce platelet-related morbidity and mortality in inflammation.

The long-term goal of the lab is to identify TPO-independent pathways of megakaryocyte maturation that result in novel therapeutics to treat platelet disorders. Current lab projects are focused on using the chemokine CCL5 and platelet extracellular vesicles to enhance megakaryopoiesis and platelet production, studying the role of megakaryocytes in the pathogenesis of autoimmune diseases such as lupus, and elucidating how lipids regulate megakaryocyte maturation and platelet production.