Howard PetrieDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL, USA F1000 Faculty Member (since 22 December 2011)
Professor of Cancer Biology
BS/MS The Pennsylvania State University
PhD The University of Nebraska Medical Center
Our research focuses on how the thymic microenvironment induces T-lineage specification and proliferation of multipotent hematopoietic progenitor/stem cells. Like all cells of hematopoietic origin, new T lymphocytes must be generated throughout life, a task that is the primary function of the thymus. Unlike other tissues that undergo steady-state differentiation, however, the thymus contains no self-renewing progenitor cells. Instead, new progenitors are specifically recruited from a pool of multi-potent progenitors that circulate within the blood. Once inside the thymus, these progenitors undergo a series of cell divisions to generate a large pool of T-lineage restricted cells that undergo selection based on the specificity of their antigen receptors, and are ultimately exported to the peripheral immune system. Our laboratory focuses on the early aspects of the intrathymic differentiation process, particularly on those aspects that relate to thymic homing, proliferative expansion, and T lineage commitment. In recent years, we have shown that different phases of these processes take place in specific tissue regions within the thymus, indicating the presence of different signaling microenvironments in the thymus and obligating the existence of a system for moving progenitors between them. We have now defined gene expression signatures that reflect the complex diversity of stromal cells in each functional subregion of the thymus and that define each sub-region. Among these, we can identify stromal-lymphoid as well as stromal-stromal interactions, as well as gaining ket insights into the biology of stromal cells themselves.
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