PhD, University of Iowa
Area of Interest
The Ellis laboratory is investigating the molecular basis of the bone marrow failure syndrome, Diamond Blackfan anemia (DBA). DBA patients typically have a red blood cell hypoplasia, a heterogeneous collection of developmental abnormalities, and a predisposition to cancer. DBA is the first human disease linked to mutations in genes encoding ribosomal proteins. The first of these genes identified, RPS19, is mutated in approximately 25% of DBA patients. Our laboratory has shown that both yeast and human Rps19 proteins are required for the biogenesis of 40S ribosomal subunits. We have also detected a signature for Rps19 dysfunction in the bone marrow of DBA patients with mutations in RPS19. Recently we have collaborated with a group in Boston to show that a ribosomal proteins gene deleted in the 5q- subtype of myelodysplastic syndrome is responsible for the refractory anemia associated with this disease. We have also collaborated with a group at Johns Hopkins University to show that DBA can be caused by mutations in a gene encoding a large subunit ribosomal protein. These data firmly establish DBA as a ribosome-based disease and point to the exquisite sensitivity of erythropoietic progenitor cells to diminished ribosome levels. The Ellis laboratory also studies a second bone marrow failure syndrome, Shwachman Diamond syndrome, which has been linked to defects in ribosome synthesis.
Lipton JM, Ellis SR. (2009) Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am. 2009 Apr;23(2):261-82. Review.
Nihrane A, Sezgin G, Dsilva S, Dellorusso P, Yamamoto K, Ellis SR, Liu JM. (2009) Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A. Blood Cells Mol Dis. 2009 Jan-Feb;42(1):85-91. Epub 2008 Nov 17.
Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC Jr, 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. (2008) Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008 Sep 1;112(5):1582-92. Epub 2008 Jun 5.
Ebert BL, Pretz J, Bosco J, Chang CY, Tamayo P, Galili N, Raza A, Root DE, Attar E, Ellis SR, Golub TR. (2008) Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature. 2008 Jan 17;451(7176):335-9.
Ellis SR and Lipton JM. (2008) Diamond Blackfan Anemia: A Disorder of Red Cell Development. Curr. Top. Cell. Biol. 82, 217-241
Ebert BL, Pretz J, Bosco J, Chang CY, Tamayo P, Galili N, Raza A, Root DE, Attar E, Ellis SR, and Golub TR. (2008) Identification of RPS14 as a 5q- syndrome gene by RNA interference. Nature 451, 335-339
Liu JM and Ellis SR. (2006) Ribosomes and marrow failure: coincidental association or molecular paradigm. Blood 107, 4583-4588
Flygare J, Aspesi A, Bailey JC, Miyake K, Caffrey JM, Karlsson S, and Ellis SR. (2006) Human RPS19 the gene mutated in Diamond Blackfan Anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood 109, 980-986
Ellis SR, and Massey AT. (2006) Diamond Blackfan Anemia: A paradigm for a ribosome-based disease. Med. Hypotheses 66, 643-648
Léger-Silvestre I, Caffrey JM, Dawaliby R, Arias-Alvares D, Gas N, Bertolone SJ, Gleizes PE and Ellis SR. (2005) Specific Role for yeast homologs Diamond Blackfan Anemia Rps19 protein in ribosome synthesis. J. Biol. Chem. 280, 38177-38185