Research Overview

Dr. Gazda’s laboratory studies molecular causes and pathothysiology of DBA and developed mouse models of DBA with the goal of finding the better treatment than what is currently available for DBA patients.

Her laboratory closely collaborates with several researchers from Boston Children’s Hospital and international institutions.

Laborator Projects

  1. Diamond-Blackfan anemia gene discovery:Using high-throughput genetic screening, array comparative genomic hybridization and whole exome sequencing, we identified mutations in ten (nine ribosomal protein genes and GATA1) out of eighteen DBA genes. However, ~35% of DBA patients still do not have a molecular diagnosis. We plan to perform whole genome sequencing on samples from whole exome sequencing unsolved DBA families to identify the remaining genes whose mutations are responsible for DBA.

  2. Drug discovery for Diamond-Blackfan anemia:Sankaran’s laboratory and our group demonstrated that decreased GATA1 translation underlies Diamond-Blackfan anemia in ribosomal protein gene mutated patients. We have also generated RPL5 deficient mice using transgenic RNAi interference (shRNA Rpl5 ). The doxycycline treated shRNA Rpl5 mice exhibit anemia mimicking DBA and have decreased GATA 1 level in erythroid bone marrow cells. We want to search for compounds that can increase GATA1 expression in bone marrow erythroid cells from these mice. We hope that positive hits applied in vivo will ameliorate anemia in shRNA Rpl5 mice and subsequently in patients with DBA.

  3. Mechanism of sarcoma in DBA:Recent studies conducted by the DBA Registry of North America revealed that the relative risk of cancer in DBA was increased 5.4 fold compared to the general population. Our study on mouse models of DBA revealed increased incidence of soft tissue sarcoma and osteosarcoma compared to wild type mice. We study the mechanism of sarcoma in Rps24+/- and Rpl5 +/- mice to shed light on mechanism of sarcoma in DBA patients.

About Hanna T. Gazda

Dr. Gazda obtained her M.D. and Ph.D. degrees from the Medical University of Warsaw, Poland. Following Pediatric residency in Poland, she moved to the Unites States for a postdoctoral fellowship at Dana-Farber Cancer Institute where she studied genetic causes of Diamond-Blackfan anemia (DBA), a congenital hypoplastic anemia and a broad developmental disease that usually presents early in infancy and is associated with birth defects and increased likelihood of developing malignancy. She then moved to Boston Children’s Hospital where she continued her studies on molecular causes and pathogenesis of DBA. Her work on genetic causes of DBA reinforced the notion that DBA is a ribosomal disease. She established her own laboratory at Boston Children’s Hospital in 2010 and she is presently an Assistant Professor at Harvard University.

Selected Publications

Ludwig LS, Gazda HT, Eng JC, Eichhorn SW, Thiru P, Ghazvinian R, George TI, Gotlib JR, Beggs AH, Sieff CA, Lodish HF, Lander ES, Sankaran VG. Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med. 2014; 20:748-53.

Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio J-A, Beggs AH, Sieff CA, Orkin SH, Nathan DG, Lander ES, Gazda HT. Exome Sequencing Identifies GATA1 Mutations Resulting in Diamond-Blackfan Anemia. J Clin Invest. 2012; 122:2439-43.

Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, Schneider HE, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Glader B, Arceci RJ, Farrar JE, Atsidaftos E, Lipton JM, Gleizes PE, Gazda HT. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010;86:222-8.

Researcher Services

Researcher Areas

  • Diamond-Blackfan Anemia (DBA)

Research Departments

Research Divisions

Researcher Centers

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, Abdulhay NJ, Specht H, Keshishian H, Mani DR, Jovanovic M, Ellis SR, Fulco CP, Engreitz JM, Schütz S, Lian J, Gripp KW, Weinberg OK, Pinkus GS, Gehrke L, Regev A, Lander ES, Gazda HT, Lee WY, Panse VG, Carr SA, Sankaran VG. Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis. Cell. 2018 Mar 22; 173(1):90-103.e19. View abstract
  2. Chakraborty A, Uechi T, Nakajima Y, Gazda HT, O'Donohue MF, Gleizes PE, Kenmochi N. Cross talk between TP53 and c-Myc in the pathophysiology of Diamond-Blackfan anemia: Evidence from RPL11-deficient in vivo and in vitro models. Biochem Biophys Res Commun. 2018 01 08; 495(2):1839-1845. View abstract
  3. Kim AR, Ulirsch JC, Wilmes S, Unal E, Moraga I, Karakukcu M, Yuan D, Kazerounian S, Abdulhay NJ, King DS, Gupta N, Gabriel SB, Lander ES, Patiroglu T, Ozcan A, Ozdemir MA, Garcia KC, Piehler J, Gazda HT, Klein DE, Sankaran VG. Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. Cell. 2017 03 09; 168(6):1053-1064.e15. View abstract
  4. Doulatov S, Vo LT, Macari ER, Wahlster L, Kinney MA, Taylor AM, Barragan J, Gupta M, McGrath K, Lee HY, Humphries JM, DeVine A, Narla A, Alter BP, Beggs AH, Agarwal S, Ebert BL, Gazda HT, Lodish HF, Sieff CA, Schlaeger TM, Zon LI, Daley GQ. Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors. Sci Transl Med. 2017 02 08; 9(376). View abstract
  5. Narla A, Yuan D, Kazerounian S, LaVasseur C, Ulirsch JC, Narla J, Glader B, Sankaran VG, Gazda H. A novel pathogenic mutation in RPL11 identified in a patient diagnosed with diamond Blackfan anemia as a young adult. Blood Cells Mol Dis. 2016 10; 61:46-7. View abstract
  6. Kazerounian S, Ciarlini PD, Yuan D, Ghazvinian R, Alberich-Jorda M, Joshi M, Zhang H, Beggs AH, Gazda HT. Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice. J Cancer. 2016; 7(1):32-6. View abstract
  7. Danilova N, Gazda HT. Ribosomopathies: how a common root can cause a tree of pathologies. Dis Model Mech. 2015 Sep; 8(9):1013-26. View abstract
  8. Ludwig LS, Gazda HT, Eng JC, Eichhorn SW, Thiru P, Ghazvinian R, George TI, Gotlib JR, Beggs AH, Sieff CA, Lodish HF, Lander ES, Sankaran VG. Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med. 2014 Jul; 20(7):748-53. View abstract
  9. Heijnen HF, van Wijk R, Pereboom TC, Goos YJ, Seinen CW, van Oirschot BA, van Dooren R, Gastou M, Giles RH, van Solinge W, Kuijpers TW, Gazda HT, Bierings MB, Da Costa L, MacInnes AW. Ribosomal protein mutations induce autophagy through S6 kinase inhibition of the insulin pathway. PLoS Genet. 2014; 10(5):e1004371. View abstract
  10. Klar J, Khalfallah A, Arzoo PS, Gazda HT, Dahl N. Recurrent GATA1 mutations in Diamond-Blackfan anaemia. Br J Haematol. 2014 Sep; 166(6):949-51. View abstract
  11. Gagne KE, Ghazvinian R, Yuan D, Zon RL, Storm K, Mazur-Popinska M, Andolina L, Bubala H, Golebiowska S, Higman MA, Kalwak K, Kurre P, Matysiak M, Niewiadomska E, Pels S, Petruzzi MJ, Pobudejska-Pieniazek A, Szczepanski T, Fleming MD, Gazda HT, Agarwal S. Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood. 2014 Jul 17; 124(3):437-40. View abstract
  12. Pereboom TC, Bondt A, Pallaki P, Klasson TD, Goos YJ, Essers PB, Groot Koerkamp MJ, Gazda HT, Holstege FC, Costa LD, MacInnes AW. Translation of branched-chain aminotransferase-1 transcripts is impaired in cells haploinsufficient for ribosomal protein genes. Exp Hematol. 2014 May; 42(5):394-403.e4. View abstract
  13. Vlachos A, Farrar JE, Atsidaftos E, Muir E, Narla A, Markello TC, Singh SA, Landowski M, Gazda HT, Blanc L, Liu JM, Ellis SR, Arceci RJ, Ebert BL, Bodine DM, Lipton JM. Diminutive somatic deletions in the 5q region lead to a phenotype atypical of classical 5q- syndrome. Blood. 2013 Oct 03; 122(14):2487-90. View abstract
  14. Landowski M, O'Donohue MF, Buros C, Ghazvinian R, Montel-Lehry N, Vlachos A, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Glader B, Atsidaftos E, Lipton JM, Beggs AH, Gleizes PE, Gazda HT. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum Genet. 2013 Nov; 132(11):1265-74. View abstract
  15. Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio JA, Beggs AH, Sieff CA, Orkin SH, Nathan DG, Lander ES, Gazda HT. Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest. 2012 Jul; 122(7):2439-43. View abstract
  16. Gazda HT, Preti M, Sheen MR, O'Donohue MF, Vlachos A, Davies SM, Kattamis A, Doherty L, Landowski M, Buros C, Ghazvinian R, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Glader B, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia. Hum Mutat. 2012 Jul; 33(7):1037-44. View abstract
  17. Payne EM, Bolli N, Rhodes J, Abdel-Wahab OI, Levine R, Hedvat CV, Stone R, Khanna-Gupta A, Sun H, Kanki JP, Gazda HT, Beggs AH, Cotter FE, Look AT. Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML. Blood. 2011 Jul 28; 118(4):903-15. View abstract
  18. Boria I, Garelli E, Gazda HT, Aspesi A, Quarello P, Pavesi E, Ferrante D, Meerpohl JJ, Kartal M, Da Costa L, Proust A, Leblanc T, Simansour M, Dahl N, Fröjmark AS, Pospisilova D, Cmejla R, Beggs AH, Sheen MR, Landowski M, Buros CM, Clinton CM, Dobson LJ, Vlachos A, Atsidaftos E, Lipton JM, Ellis SR, Ramenghi U, Dianzani I. The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update. Hum Mutat. 2010 Dec; 31(12):1269-79. View abstract
  19. Crétien A, Proust A, Delaunay J, Rincé P, Leblanc T, Ducrocq R, Simansour M, Marie I, Tamary H, Meerpohl J, Niemeyer C, Gazda H, Sieff C, Ball S, Tchernia G, Mohandas N, Da Costa L. Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan anemia: potential implications for phenotypic heterogeneity. Am J Hematol. 2010 Feb; 85(2):111-6. View abstract
  20. Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, Schneider HE, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Glader B, Arceci RJ, Farrar JE, Atsidaftos E, Lipton JM, Gleizes PE, Gazda HT. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010 Feb 12; 86(2):222-8. View abstract
  21. Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec; 83(6):769-80. View abstract
  22. Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC, Meltzer P, Esposito D, Beggs AH, Schneider HE, Grabowska A, Ball SE, Niewiadomska E, Sieff CA, Vlachos A, Atsidaftos E, Ellis SR, Lipton JM, Gazda HT, Arceci RJ. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008 Sep 01; 112(5):1582-92. View abstract
  23. Choesmel V, Fribourg S, Aguissa-Touré AH, Pinaud N, Legrand P, Gazda HT, Gleizes PE. Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum Mol Genet. 2008 May 01; 17(9):1253-63. View abstract
  24. Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006 Dec; 79(6):1110-8. View abstract
  25. Gazda HT, Sieff CA. Recent insights into the pathogenesis of Diamond-Blackfan anaemia. Br J Haematol. 2006 Oct; 135(2):149-57. View abstract
  26. Gazda HT, Kho AT, Sanoudou D, Zaucha JM, Kohane IS, Sieff CA, Beggs AH. Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells. 2006 Sep; 24(9):2034-44. View abstract
  27. Quigley JG, Gazda H, Yang Z, Ball S, Sieff CA, Abkowitz JL. Investigation of a putative role for FLVCR, a cytoplasmic heme exporter, in Diamond-Blackfan anemia. Blood Cells Mol Dis. 2005 Sep-Oct; 35(2):189-92. View abstract
  28. 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 anaemia patients with RPS19 mutations. Br J Haematol. 2004 Oct; 127(1):105-13. View abstract
  29. Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH. Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proc Natl Acad Sci U S A. 2003 Apr 15; 100(8):4666-71. View abstract
  30. Zervos A, Hunt KE, Tong HQ, Avallone J, Morales J, Friedman N, Cohen BH, Clark B, Guo S, Gazda H, Beggs AH, Traboulsi EI. Clinical, genetic and histopathologic findings in two siblings with muscle-eye-brain disease. Eur J Ophthalmol. 2002 Jul-Aug; 12(4):253-61. View abstract
  31. Gazda H, Lipton JM, Willig TN, Ball S, Niemeyer CM, Tchernia G, Mohandas N, Daly MJ, Ploszynska A, Orfali KA, Vlachos A, Glader BE, Rokicka-Milewska R, Ohara A, Baker D, Pospisilova D, Webber A, Viskochil DH, Nathan DG, Beggs AH, Sieff CA. Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood. 2001 Apr 01; 97(7):2145-50. View abstract
  32. Wulff K, Gazda H, Schröder W, Robicka-Milewska R, Herrmann FH. Identification of a novel large F9 gene mutation-an insertion of an Alu repeated DNA element in exon e of the factor 9 gene. Hum Mutat. 2000 Mar; 15(3):299. View abstract
  33. Willig TN, Gazda H, Sieff CA. Diamond-Blackfan anemia. Curr Opin Hematol. 2000 Mar; 7(2):85-94. View abstract
  34. Schröder W, Poetsch M, Gazda H, Werner W, Reichelt T, Knoll W, Rokicka-Milewska R, Zieleniewska B, Herrmann FH. A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case report. Br J Haematol. 1998 Mar; 100(4):750-7. View abstract
  35. Gazda H, Grabowska A. [Topical treatment of oral bleeding in children with clotting disturbances]. Wiad Lek. 1993 Feb; 46(3-4):111-5. View abstract
  36. Klukowska A, Gazda H, Szczepanik E. [Remote results of the treatment of intracranial hemorrhage in children with congenital hemorrhagic diathesis]. Pediatr Pol. 1988 May; 63(5):312-8. View abstract
  37. Peterlik M, Gazda H. Sodium-linked transport of ethacrynic acid by rat liver: possible significance for choleretic action. Biochem Pharmacol. 1980 Oct 15; 29(20):2733-9. View abstract