Imaging cell homing and engraftment in the bone marrow

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DESCRIPTION (provided by applicant): The goal of this proposal is to prepare the candidate for an academic research career in Hematology and Oncology. The candidate is an M.D., Ph.D. who earned a doctoral degree in Cancer Biology developing receptor-targeted contrast agents for magnetic resonance imaging. She has recently completed the clinical phase of fellowship training, and is now pursuing further research training in the laboratory of Dr. David Scadden, director of Experimental Hematology and of Hematologic Malignancies at the Massachusetts General Hospital and Harvard Medical School. Dr. Scadden is a highly-regarded leader in hematopoietic stem cell research with extensive experience in mentoring trainees. His laboratory will provide an ideal environment for the candidate to learn a broad range of molecular and cellular biology techniques as well as gain further proficiency in the conduct of clinically relevant research. In addition, the candidate will continue a collaboration with Dr. Charles Lin of the Wellman Laboratories of Photomedicine, who will provide substantial expertise and resources in molecular imaging. These laboratories, and the MGH Cancer Center, will offer a rich intellectual environment ideal for scientific development, with multiple opportunities for scientific interaction, educational seminars, conferences and journal clubs. The proposed research seeks to define the mechanisms that govern leukemic cell homing and engraftment in the bone marrow microenvironment using real-time confocal and dual photon fluorescence imaging. To test the hypothesis that leukemic cells use tissue homing mechanisms analogous to those of their benign leukocyte counterparts, the proposed experiments will examine the signals that enable leukemic cells and hematopoietic stem cells to home to and proliferate within very specific microenvironments. Elucidation of these mechanisms could ultimately define new biologic targets for leukemia therapy that are minimally toxic to normal hematopoiesis. The specific aims of this proposal are: 1) to achieve real-time in vivo imaging of leukemic cell homing and engraftment in murine bone marrow, 2) to define the molecular basis of leukemic-vascular cell adhesion events that affect bone marrow homing, 3) to identify distinctions between leukemic and normal stem cell bone marrow homing in vivo that may provide targets for therapeutic intervention.