David G. Nathan, MD
Robert A. Stranahan Distinguished Professor of Pediatrics and Professor of Medicine, Harvard Medical School
Office phone: 617-632-2155
Preferred contact method: appointment phone
View Physician Profile
Aplastic anemia, Thalassemia, Sickle cell disease
Area of ResearchTreatment of Sickle Cell Crisis with Inhibitors of NKT cell activation RC2HL101367 2010-2012
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
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.
- John Stearns Medal for Lifetime Achievement in Medicine of the New York Academy of Medicine, 2009
- George M. Kober Medal of the Association of American Physicians, 2006
- Howland Medal of the American Pediatric Society, 2003
- Annual Award for Excellence in Clinical Research, NIH, 1996
- Henry Stratton Medal, American Society of Hematology, 1995
- National Medal of Science, 1990
ResearchTreatment of Sickle Cell Crisis with Inhibitors of NKT cell activation RC2HL101367 2010-2012
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.
- Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R, Krebs-Brown AJ, Anderson JR, Alberti D, Sizer KC, Nathan DG. Effectiveness and safety of ICL670 in iron-loaded patients with thalassemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2003;361:1597-602.
- Brittenham GM, Nathan DG, Olivieri NF, Porter JB, Pippard M, Vichinsky EP, Weatherall DJ. Deferiprone and hepatic fibrosis. Blood 2003;101:5089-90.
- Nathan DG. Determination can win the battle. Lancet 2004;364:301.
- Gratzer W, Nathan DG. Obituary: Fred S. Rosen (1930 -2005). Nature 2005;435:1044.
- Nathan DG. Clinical research: a tale of two studies.
Trans Am Clin Climatol Assoc 2003;114:219-30.
- Nathan DG. Acceptance of the 2003 John Howland Award: a journey in clinical research. Pediatr Res 2004;56:169-76.
- Nathan DG, Wilson JD. Clinical research and the NIH-a report card. N Engl J Med 2003;349:1860-5.
- Gazda HT, Zhong R, Long L, Niewiadomska E, Lipton JM, Ploszynska A, Zaucha JM, Vlachos A, Atsidaftos E, Viskochil DH, Niemeyer CM, Meerpohl JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan DG, Beggs AH, Sieff CA. RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anemia patients with RPS19 mutations. Br J Haematol 2004;127:105-13.
- Nathan DG. The several Cs of translational clinical research. J Clin Invest 2005;115:795-7.
- Cunningham MJ, Nathan DG. New developments in iron chelators. Curr Opin Hematol 2005;12:129-34.