This application seeks to amalgamate two training grants in hematology and in hemostasis and thrombosis under the new title """"""""Blood and Vascular Biology"""""""". The purpose of our program continues to be the training of MDs and Ph.Ds in basic investigational approaches to problems in hematologic research and vascular biology. We are requesting annual support for 6 postdoctoral trainees. MDs will have completed general training as well as hematology/oncology clinical training and will have expressed a firm commitment to a career in academic medicine. Ph.Ds may be accepted immediately after receipt of their degree. Trainees will devote 2-3 years to full-time laboratory research, supplemented by frequent formal and informal research meetings, seminars and journal review sessions. In a separate track, a 3.4 year training program leading to a Ph.D. will be offered to selected M.D. trainees. For those trainees additional formal course work will be required. The training faculty consists of 15 senior and 5 junior investigators occupying approximately 25,000 square feet of laboratory space. Only senior faculty will have direct responsibility for a fellow's training program, although junior faculty will be actively involved in support of fellowship training. Areas of investigation include: signalling mechanisms in platelets, megakaryocytes, endothelial cells; megakaryocyte growth and differentiation; the roles of proteoglycans and sulfated proteins in platelet function and megakaryocyte maturation; platelet kinetics, metabolism and preservation; interaction of platelets and endothelial cells with plasma hemostatic factors and adhesive proteins; structure and function of the endothelial GpIb complex; angiogenesis and gene alterations during angiogenesis; effects of hypoxia on endothelial cell gene expression; regulation of plasminogen activator inhibitor-l gene expression; mechanisms of action of lupus anticoagulants and anticardiolipin antibodies; erythropoietin function and gene expression; red cell structure and function in the hemoglobinopathies; lymphocyte structure and function, with particular reference to NK cells; immunologic tolerance and adoptive cellular immunotherapy; antisense effects on leukemic cell growth and function; the genetic basis for leukemic abnormalities. Research activities under this training grant have already been reviewed by the IRB and IACUC committee in the form of individual research grants and contracts. No new research activities will be instituted solely under this training grant. The Cardeza Foundation, the Jefferson Cancer Institute, and associated laboratories are fully equipped to carry out the research programs outlined below. In addition, resources of the Cardeza Foundation library and conference room, medical illustration unit, clinical laboratory, and administrative facilities and personnel will be available for support of this training grant.
