The long-term objective of this 5-year proposal is to provide the training necessary to embark on an academic career in Hematology/Oncology. The candidate has completed clinical fellowship training and will use the Mentored Clinical Scientist Development Award to develop critical skills necessary to pursue research in stern cell biology. Guidance and mentorship will be provided by Dr. David Scadden, Director of Experimental Hematology at the Massachusetts General Hospital, who is a recognized leader in stern cell biology. Dr. Scadden has trained numerous post-doctoral fellows who have successfully made the transition to independent academic careers. Additional mentorship will be provided by a distinguished advisory committee. The research environment will provide direct experience in experimental techniques, as well as a variety of educational seminars and collaborations. The proposed research focuses on mechanisms underlying the recruitment of primitive bone marrow derived stem/progenitor cells to tumor vasculature. Recent studies suggest that bone marrow progenitor cells can differentiate into endothelial cells and be incorporated into tumor neovasculature. Preliminary results in the Scadden laboratory suggest that tumors are able to recruit primitive bone marrow lineage negative stem/progenitor cells. However, mechanisms underlying stern cell recruitment are unknown. Chemokine/chemokine receptor pair interactions, such as stromal cell-derived factor-1 (SDF-1)/CXCR4, provide critical cues for the homing of bone marrow stem cells and other leukocytes. This proposal seeks to define the molecular basis for stem cell translocation from bone marrow to tumor vessels.
The specific aims of this proposal are: 1) to determine the role of SDF-1/CXCR4 interactions in bone marrow cell recruitment to tumors and 2) to define additional chemokine/chemokine receptor pairs that participate in this process. The laboratory of Dr. Scadden provides an ideal setting for accomplishing both the research as well as didactic training goals. Dr. Scadden has expertise in stem cell biology, and reagents necessary to define the role of chemokines in bone marrow cell homing to tumors are readily available. It is expected that at the completion of this training program, the applicant will be able to successfully continue as an independent investigator and contribute significantly to the fields of stern cell biology and cancer.
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| Aghi, Manish; Cohen, Kenneth S; Klein, Rachael J et al. (2006) Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic neovasculature, where microenvironment influences their differentiated phenotypes. Cancer Res 66:9054-64 |
