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Dr. Nathan received his MD from Harvard Medical School in 1955, and was senior resident in medicine at Peter Bent Brigham Hospital and clinical associate at the National Cancer Institute. Between 1967 and 1984, he was chief of hematology at Children's Hospital Boston (CHB), and then chief of hematology and oncology at CHB and DFCI. He chaired the Department of Pediatrics from 1985 to 1995, and served as president of DFCI until 2000.
This is a consortium grant of which I am clinical co-PI and my colleague Joel Linden of the LaJolla Institute of Allergy and Immunology is the basic science co-PI. Linden has studied sickle cell disease mice and found that inhibition of iNKT cells with either antibodies or adenosine analogues markedly improves pulmonary disease in these animals. Therefore Linden and I together with colleagues at Children's Hospital, Brigham and Women's Hospital, Beth Israel Deaconess Hospital and Washington University in St Louis have established a program in which we intend to determine whether Lexiscan, an FDA approved adenosine analogue, can be administered safely in doses capable of inhibiting iNKT cells in sickle cell anemia patients. After a satisfactory dose is determined, we will treat such patients with Lexiscan with the hope that the drug will reduce the impact of both painful vaso-occlusive crises and acute chest syndrome. We now have FDA and local IRB approval. Patient accrual should begin in March of 2010. The first experiments will be dose finding efforts. Meanwhile Linden and co-workers are searching in the laboratory for better drugs and antibodies that may be more effective than Lexiscan in blunting of the adenosine A2a receptors that richly decorate INKT cells without activating other classes of adenosine receptors on the vascular endothelial cells.
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