Robert A. Brodsky, MD

Professional Titles

• Director, Division of Hematology
• Program Director, T32 Training Program, Division of Hematology
• Johns Hopkins Family Professor of Oncology Research

Primary Academic Title

Professor of Medicine

Background

Centers and Institutes

• Heart and Vascular Institute
• Sidney Kimmel Comprehensive Cancer Center

Clinical Trial Keywords

Aplastic Anemia; Sickle Cell Anemia; Post-Transplant Cyclophosphamide

Videos

• Getting off the Ground

• Johns Hopkins Medicine: Aplastic Anemia

• A Remarkable Journey

• Sickle Cell Breakthrough | Shauna's Story

• Robert Brodsky and Half-match Bone Marrow Transplants in Sickle Cell Patients

Recent News Articles and Media Coverage

• “Sickle Cell Transplants Could See Wider Use,” The New York Times, Nov. 12, 2012

Additional Academic Titles

Professor of Oncology

Research Interests

Aplastic anemia, Assay development to diagnose PNH (FLAER) and other complementopathies (mHam), Drug development for complementopathies, Mechanisms of complement dysregulation

Lab Website

Robert Brodsky Lab

• Investigators in the Robert Brodsky Lab study normal and abnormal hematopoiesis, particularly mutations of the phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) gene in aplastic anemia. Our team has developed a new diagnostic assay for paroxysmal nocturnal hemoglobinuria (PNH) that is based on the toxin Aaeromonas hydrophila.

Research Summary

Dr. Brodsky’s clinical research involves thrombotic microangiopathies, aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and other bone marrow failure disorders. He and his colleagues have shown that HLA-haploidentical bone marrow transplant with high-dose post-transplant cyclophosphamide can cure most patients with severe aplastic anemia and hemoglobinopathies including sickle cell anemia.  Other clinical research activities involve the use of complement inhibitors to treat complementopathies such as PNH, atypical hemolytic uremic syndrome, and the HELLP syndrome.

His laboratory focuses on complement. He developed to the FLAER assay to diagnose PNH and the modified Ham (mHam) test to distinguish atypical hemolytic uremic syndrome from other thrombotic microangiopathic hemolytic anemias.  His lab has used the mHam to uncover germline complement mutations in other complementopathies such as HELLP syndrome, antiphospholipid antibody syndrome, and catastrophic antiphospholipid antibody syndrome (CAPS). Using the mHam he has shown that the SARS-CoV-2 spike protein dysregulates the alternative pathway of complement by interfering with the function of complement factor H on the cell surface. He also studies the interplay between the complement and coagulation cascades.

Selected Publications

• 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.

• 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

• Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria. Blood. 2014 [in press]

• 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.

• 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.

• 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.

• 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]

• 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.

• 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.

• 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.

• 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.

• 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]

• 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.

• Pu JJ, Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria from Bench to Bedside. Clinical and Translational Science. 2011;4(3):219-24. PMID:21707954; PMCID:PMC3128433.

• 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.

• 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.

• 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.

• 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.

• 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.

Honors

• 2013 Clinical Research Forum: Clinical Research Achievement Award for 2nd most important clinical research paper in medicine; HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease, Blood, 1/1/12
• Leukemia and Lymphoma Society of America Scholar, 1/1/00
• Junior Faculty Scholar, American Society of Hematology, 1/1/98
• Thomas E. Sandefur, Jr. Fellow in Stem Cell Research, 1/1/97
• 1st Prize, Johns Hopkins Oncology Center Fellow Research Day, 1/1/96
• American Society of Hematology Travel Award, 1/1/96
• American Society of Hematology Travel Award, 1/1/94
• Samuel Levit, M.D. Award - Outstanding Clinical and Humanitarianism in the care of Medical Patients, 1/1/89
• James P. Fullin Memorial Award - Outstanding Clinical and Academic Performance in Hematology/Oncology, 1/1/89
• Academic Honors: Oncology, 1/1/89
• Academic Distinctions: Medicine, Neurology, 1/1/89
• Chairman's Invitational Honors Program, 1/1/88

Memberships

• American College of Physicians, Fellow
• American Society of Hematology
• International Society of Experimental Hematology