Orah Platt's research focuses on sickle cell disease. She has defined the epidemiology of the major complications and has dissected the sickle red-cell membrane in an effort to find new therapeutic strategies.
Recently, in collaboration with Carlos Brugnara, she has demonstrated that the antifungal clotrimazole can block dehydration, and ameliorate sickling of red blood cells. ICA-17043, a drug developed on a metabolite of clotrimazole, has been readied for Phase III trials in treating sickle-cell disease.
Research Background
Orah Platt received her MD degree from Harvard Medical School. She completed an internship and a residency at Massachusetts General Hospital and a fellowship at Children's Hospital Boston. Dr. Dr. Platt is Master of the William Bosworth Castle Society at Harvard Medical School and has been honored with numerous awards for teaching and mentoring.
Education
Internship
Massachusetts General Hospital
Boston
MA
Medical School
Harvard Medical School
Boston
MA
Residency
Massachusetts General Hospital
Boston
MA
Fellowship
Boston Children's Hospital
Boston
MA
Publications
Heritability of fetal hemoglobin, white cell count, and other clinical traits from a sickle cell disease family cohort. Am J Hematol. 2019 05; 94(5):522-527. View Abstract
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature. 2011 Aug 31; 478(7367):97-102. View Abstract
Age- and gender-dependent obesity in individuals with 16p11.2 deletion. J Genet Genomics. 2011 Sep 20; 38(9):403-9. View Abstract
Abnormal modulation of cell protective systems in response to ischemic/reperfusion injury is important in the development of mouse sickle cell hepatopathy. Haematologica. 2011 Jan; 96(1):24-32. View Abstract
Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010 Aug 05; 116(5):687-92. View Abstract
Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss. Physiol Genomics. 2009 Aug 07; 38(3):281-90. View Abstract
SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008 Aug; 10(8):586-92. View Abstract
Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med. 2008 Mar 27; 358(13):1362-9. View Abstract
Protective effects of phosphodiesterase-4 (PDE-4) inhibition in the early phase of pulmonary arterial hypertension in transgenic sickle cell mice. FASEB J. 2008 Jun; 22(6):1849-60. View Abstract
Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008 Feb 14; 358(7):667-75. View Abstract
Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance. Clin Chem. 2007 Dec; 53(12):2051-9. View Abstract
Quantitative trait loci for peripheral blood cell counts: a study in baboons. Mamm Genome. 2007 May; 18(5):361-72. View Abstract
Quantitative trait loci for baseline erythroid traits. Mamm Genome. 2006 Apr; 17(4):298-309. View Abstract
Prevention and management of stroke in sickle cell anemia. Hematology Am Soc Hematol Educ Program. 2006; 54-7. View Abstract
Preventing stroke in sickle cell anemia. N Engl J Med. 2005 Dec 29; 353(26):2743-5. View Abstract
Quantitative trait loci for baseline white blood cell count, platelet count, and mean platelet volume. Mamm Genome. 2005 Oct; 16(10):749-63. View Abstract
Genetic influences on peripheral blood cell counts: a study in baboons. Blood. 2005 Aug 15; 106(4):1210-4. View Abstract
Acquisition of mutans streptococci and caries prevalence in pediatric sickle cell anemia patients receiving long-term antibiotic therapy. Pediatr Dent. 2005 May-Jun; 27(3):186-90. View Abstract
Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342 kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness. Am J Med Genet A. 2003 Aug 30; 121A(2):102-8. View Abstract
Human erythrocyte membrane band 3 protein influences hemoglobin cooperativity. Possible effect on oxygen transport. J Biol Chem. 2003 Oct 10; 278(41):39565-71. View Abstract
Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing. Genet Med. 2002 Jul-Aug; 4(4):279-88. View Abstract
Sickle cell anemia as an inflammatory disease. J Clin Invest. 2000 Aug; 106(3):337-8. View Abstract
The acute chest syndrome of sickle cell disease. N Engl J Med. 2000 Jun 22; 342(25):1904-7. View Abstract
Transposing sequences between fetal and adult hemoglobins indicates which subunits and regulatory molecule interfaces are functionally related. Biochemistry. 2000 Apr 04; 39(13):3774-81. View Abstract
Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999 Sep 01; 94(5):1550-4. View Abstract
Reticulocyte hemoglobin content to diagnose iron deficiency in children. JAMA. 1999 Jun 16; 281(23):2225-30. View Abstract
Silent cerebral infarcts in sickle cell anemia: a risk factor analysis. The Cooperative Study of Sickle Cell Disease. Pediatrics. 1999 Mar; 103(3):640-5. View Abstract
Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease. J Clin Invest. 1997 Oct 01; 100(7):1847-52. View Abstract
Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. Am J Clin Pathol. 1997 Aug; 108(2):133-42. View Abstract
The febrile child with sickle cell disease: a pediatrician's quandary. J Pediatr. 1997 May; 130(5):693-4. View Abstract
Bone marrow transplantation in sickle cell anemia--the dilemma of choice. N Engl J Med. 1996 Aug 08; 335(6):426-8. View Abstract
Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J Clin Invest. 1996 Mar 01; 97(5):1227-34. View Abstract
A high-performance liquid chromatographic assay for the determination of itraconazole concentration using solid-phase extraction and small sample volume. Ther Drug Monit. 1995 Oct; 17(5):522-5. View Abstract
Membrane protein interactions in sickle red blood cells: evidence of abnormal protein 3 function. Blood. 1995 Sep 01; 86(5):1992-8. View Abstract
A new therapeutic approach for sickle cell disease. Blockade of the red cell Ca(2+)-activated K+ channel by clotrimazole. Ann N Y Acad Sci. 1995 Jul 12; 763:262-71. View Abstract
Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity. J Pharmacol Exp Ther. 1995 Apr; 273(1):266-72. View Abstract
HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent. Clin Chem. 1995 Mar; 41(3):387-91. View Abstract
Sickle reticulocytes adhere to VCAM-1. Blood. 1995 Jan 01; 85(1):268-74. View Abstract
Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 09; 330(23):1639-44. View Abstract
Reticulocyte hemoglobin content (CHr): early indicator of iron deficiency and response to therapy. Blood. 1994 May 15; 83(10):3100-1. View Abstract
Easing the suffering caused by sickle cell disease. N Engl J Med. 1994 Mar 17; 330(11):783-4. View Abstract
Predicting medical student success in a clinical clerkship by rating students' nonverbal behavior. Arch Pediatr Adolesc Med. 1994 Feb; 148(2):213-9. View Abstract
A highly conserved region of human erythrocyte ankyrin contains the capacity to bind spectrin. J Biol Chem. 1993 Nov 15; 268(32):24421-6. View Abstract
Effect of context on the rating of students by faculty and housestaff in a clinical clerkship. Acad Med. 1992 Jul; 67(7):485. View Abstract
Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood. 1992 May 15; 79(10):2555-65. View Abstract
Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 04; 325(1):11-6. View Abstract
Toad urinary bladder epithelial cells contain an analogue of cytoskeletal protein 4.1. Am J Physiol. 1991 Jun; 260(6 Pt 1):C1308-14. View Abstract
Reliability of Tanner stage assessments in a multi-center study. Am J Hum Biol. 1990; 2(5):503-510. View Abstract
Pathology of membrane proteins in sickle erythrocytes. Ann N Y Acad Sci. 1989; 565:83-5. View Abstract
Is there treatment for sickle cell anemia? N Engl J Med. 1988 Dec 01; 319(22):1479-80. View Abstract
Membrane protein lesions in erythrocytes with Heinz bodies. J Clin Invest. 1988 Sep; 82(3):1051-8. View Abstract
Influence of hydroxyurea on fetal hemoglobin production in vitro. Blood. 1987 Dec; 70(6):1824-9. View Abstract
Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes. J Clin Invest. 1986 Dec; 78(6):1487-96. View Abstract
Pyruvate kinase deficiency in dog and human erythrocytes: effects of energy depletion on cation composition and cellular hydration. Am J Hematol. 1986 Nov; 23(3):217-21. View Abstract
Variant chronic granulomatous disease: modulation of the neutrophil defect by severe infection. Blood. 1986 Oct; 68(4):914-9. View Abstract
Mammalian reticulocytes lose adhesion to fibronectin during maturation to erythrocytes. Proc Natl Acad Sci U S A. 1985 Jan; 82(2):440-4. View Abstract
Loss of adhesion of erythrocyte precursors to fibronectin during erythroid differentiation. Prog Clin Biol Res. 1985; 184:355-68. View Abstract
Molecular defect in the sickle erythrocyte skeleton. Abnormal spectrin binding to sickle inside-our vesicles. J Clin Invest. 1985 Jan; 75(1):266-71. View Abstract
Chemotherapy to increase fetal hemoglobin in patients with sickle cell anemia. Am J Pediatr Hematol Oncol. 1985; 7(3):258-60. View Abstract
Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984 Aug; 74(2):652-6. View Abstract
Influence of sickle hemoglobinopathies on growth and development. N Engl J Med. 1984 Jul 05; 311(1):7-12. View Abstract
Hydroxyurea increases fetal hemoglobin production in sickle cell anemia. Trans Assoc Am Physicians. 1984; 97:268-74. View Abstract
Exercise-induced hemolysis in sickle cell anemia: shear sensitivity and erythrocyte dehydration. Blood. 1982 May; 59(5):1055-60. View Abstract
Exercise-induced hemolysis in xerocytosis. Erythrocyte dehydration and shear sensitivity. J Clin Invest. 1981 Sep; 68(3):631-8. View Abstract
Glycosylation of variant hemoglobins in normal and diabetic subjects. Diabetes Care. 1980 Sep-Oct; 3(5):590-3. View Abstract
Isobutyl nitrite toxicity by ingestion. Ann Intern Med. 1980 May; 92(5):637-8. View Abstract
Lung function in children with sickle cell anemia. Am Rev Respir Dis. 1979 Jul; 120(1):210-4. View Abstract
Newborn bleeding disorders: a practical approach. Pediatr Ann. 1979 Jun; 8(6):55-67. View Abstract
Energy reserve and cation composition of irreversibly sickled cells in vivo. Br J Haematol. 1978 Dec; 40(4):527-32. View Abstract
Red blood cell size and glycolytic enzyme activity: relationship to number of intramedullary cell divisions. Pediatr Res. 1978 Apr; 12(4 Pt 1):308-9. View Abstract