Research Summary
Dr. Brodsky's major clinical research involves the study of aplastic anemia, paroxysmal nocturnal hemoglobinuria and other bone marrow failure disorders. His research shows that immunoablative doses of cyclophosphamide, without bone marrow transplantation, can lead to durable complete remissions in severe aplastic anemia. The reason high-dose cyclophosphamide is able to ablate the effector cells without destroying hematopoietic stem cells is that the earliest stem cells (but not lymphocytes) contain high levels of aldehyde dehydrogenase conferring resistance to the cytoxic properties of cyclophosphamide. Dr. Brodsky and his colleagues in neurology and rheumatology are applying this approach in other severe autoimmune disorders including, scleroderma, myasthenia gravis, multiple sclerosis and autoimmune hematologic disorders.
Dr. Brodsky's major laboratory interests relate to the study of normal and abnormal hematopoiesis. Specifically his lab studies PIG-A gene mutations in aplastic anemia. His group has developed a novel diagnostic assay for PNH based on the pore forming toxin (aeromonas hydrophila).
Clinical Trial Keywords
aplastic anemia, high-dose cyclophosphamide
Selected Publications
Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria. Blood. 2014 [in press]
DeZern AE, Uknis M, Yuan X, Mukhina GL, Varela J, Saye J, Pu J, Brodsky RA. Complement blockade with a C1 esterase inhibitor in paroxysmal nocturnal hemoglobinuria. Exp Hematol. 2014. pii: S0301-472X(14)00241-0. PMID: 25034232 [Epub ahead of print]
Park JC, Pratz CF, Tesfaye A, Brodsky RA, Antonarakis ES. The Effect of Therapeutic Anticoagulation on Overall Survival in Men Receiving First-Line Docetaxel Chemotherapy for Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer. 2014. pii: S1558-7673(14)00118-9. PMID: 24999166 [Epub ahead of print]
Smith C, Gore A, Yan W, Abalde-Atristain L, Li Z, He C, Wang Y, Brodsky RA, Zhang K, Cheng L, Ye Z. Whole-Genome sequencing analysis reveals high specificity of CRISPR/Cas9 and TALEN-Based genome editing in human iPSCs. Cell Stem Cell 2014;15(1):12-3. PMID: 24996165.
Showel MM, Brodsky RA, Tsai HL, Briel KM, Kowalski J, Griffin CA, Jones RJ. Isolated Clonal Cytogenetic Abnormalities after High-Dose Therapy. Biol Blood Marrow Transplant 2014;20(8):1130-8. PMID: 24732780.
DeZern AE, Symons HJ, Resar LS, Borowitz MJ, Armanios MY, Brodsky RA. Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes. Eur J Haematol. 2014:92(6):467-70. PMID: 24612308.
Schrezenmeier H, Muus P, Socié G, Szer J, Urbano-Ispizua A, Maciejewski JP, Brodsky RA, Bessler M, Kanakura Y, Rosse W, Khursigara G, Bedrosian C, Hillmen P. Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry. Haematologica. 2014;99(5):922-9. PMID: 24488565; PMCID: PMC4008114.
Belet S, Fieremans N, Yuan X, Van Esch H, Verbeeck J, Ye Z, Cheng L, Brodsky BR, Hu H, Kalscheuer VM, Brodsky RA, Froyen G. Early Frameshift Mutation in PIGA Identified in a Large XLID Family Without Neonatal Lethality. Hum Mutat. 2014;35(3):350-5. PMID: 24357517.
Varela JC, Brodsky RA. Paroxysmal nocturnal hemoglobinuria and the age of therapeutic complement inhibition. Expert Rev Clin Immunol. 2013;9(11):1113-24. PMID: 24168416.
Yuan X, Braunstein E, Ye Z, Liu C, Chen G, Zhou J, Cheng L, Brodsky RA. Generation of GPI anchor protein deficient blood celss from human induced pluripotent stem cells. Stem Cells Translational Medicine. 2013; 2(11):819-29. PMID: 24113066; PMCID: PMC3808197.
DeZern AE, Pu J, McDevitt MA, Jones RJ, Brodsky RA. Burst-Forming Unit-Erythroid Assays (BFU-E) To Distinguish Cellular Bone Marrow Failure Disorders. Exp Hematology. 2013;41(9):808-16. PMID: 23660070; PMCID: PMC3769493.
Peter Hillmen, Petra Muus, Alexander Röth, Modupe O. Elebute, Antonio M. Risitano, Hubert Schrezenmeier, Jeffrey Szer, Paul Browne, Jaroslaw P. Maciejewski, Jörg Schubert, Alvaro Urbano-Ispizua, Carlos de Castro, Gérard Socié, Robert A. Brodsky. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013; 162(1):62-73. PMID: 23617322; PMCID: PMC3744747.
DeZern AE, Styler MJ, Drachman D, Hummers L, Jones RJ, Brodsky RA. Repeated treatment for severe autoimmune diseases with high dose cyclophosphomide. American Journal of Blood Research. 2013;3(1):84-90. PMID: 23358715; PMCID: PMC3555191.
Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, et al. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013;54(3):483-90. PMID: 22835045.
Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ, Brodsky RA. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120(22):4285-9. PMID: 22955919; PMCID: PMC3507140
Pu JJ, Hu R, Mukhina GL, Carraway HE, McDevitt MA, Brodsky RA. The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells. Haematologica. 2012;97(8):1225-33. PMID: 22315493; PMCID: PMC3409821.
Johnston JJ, Gropman AL, Sapp JC, Teer JK, Martin JM, Liu CF, Yuan X, Ye Z, Cheng L, Brodsky RA, Biesecker LG. The Phenotype of A Germline Mutation in PIGA: The Gene Somatically Mutated in Paroxysmal Nocturnal Hemoglobinuria. Am J Hum Genet. 2012;90(2):295-300. PMID: 22305531.
Harrison DM, Gladstone DE, Hammond E, Cheng J, Jones RJ, Brodsky RA, Kerr D, McArthur JC, Kaplin A. Treatment of relapsing-remitting multiple sclerosis with highdose cyclophosphamide induction followed by glatiramer acetate maintenance. Mult Scler. 2012; 18(2):202-9. PMID 21865410.
Gladstone DE, Bolanos-Meade J, Huff CA, Zahurak M, Flinn I, Borrello I, Luznik L, Fuchs E, Kasamon Y, Matsui W, Powell J, Levitsky H, Brodsky RA, Ambinder R, Jones RJ, Swinnen LJ. High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. Leuk Lymphoma. 2011; 52(11):2076-81. PMID: 21756035.
Pu JJ, Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria from Bench to Bedside. Clinical and Translational Science. 2011;4(3):219-24. PMID:21707954; PMCID:PMC3128433.
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