Defining the Mechanisms by Which Plateletes Regulate Angiogenesis

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DESCRIPTION (provided by applicant): The proposal entails a 5 year career development plan for attaining an academic career in Hematology. The principle investigator has completed both residency in Internal Medicine and Hematology/Oncology Fellowship and now is expanding her research skills through a project with both basic science and translational aspects. The project is an integration of the fields of platelet biology and angiogenesis. Dr. Joseph Italiano and Dr. Nancy Berliner will act as co-mentors for the principal investigator. Dr. Italiano is a well recognized leader in the field of megakaryocyte and platelet biology. To enhance the academic mentoring aspects of the program, Dr. Nancy Berliner, Chair of the Division of Hematology at Brigham and Women's Hospital (BWH) will serve as a co-mentor. In addition to her role as Director, she has a long-term expertise in myelopoiesis and has mentored a large number of young investigators. In addition, the principle investigator has assembled an advisory committee with varied scientific and clinical interests to provide scientific and academic career advice. The project will focus on the role of the platelet in angiogenesis. Recent evidence suggests that platelets organize angiogenic regulatory proteins into pharmacologically and morphologically distinct populations of alpha granules, which are then susceptible to differential regulation upon platelet activation. This proposal will entail establishing the organization of angiogenic regulatory proteins in alpha granules and understanding mechanisms of differential release. The angiogenic balance within platelet granules will also be investigated in patients with malignancy as well as those receiving anti-angiogenic therapies. The specific aims are: 1. To define how angiogenesis regulatory proteins are sequestered and stored in platelets; 2. To investigate the mechanisms by which these proteins undergo differential release; and 3. To investigate the role of the platelet in storage, delivery, and function of ant-angiogenic therapy. RELEVANCE (See instructions): Platelets are known to carry a number of proteins important in the process of growing blood vessels termed angiogenesis. In this grant we try to determine how platelets organize the proteins, regulate angiogenesis, and how these processes differ in patients with malignancy in which angiogenesis is instrumental for tumor growth. (End of Abstract)