Dr. Ebert's laboratory studies the biology and genetics of hematologic malignancies and other hematologic disorders. His group employs a range of genomic and proteomic technologies, as well as classical cellular and molecular biology approaches, to investigate the molecular basis of specific human diseases.
Major focuses of the laboratory are myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Dr. Ebert identified a gene that plays a central role in the pahtophysiology of MDS with deletions of chromosome 5q. These findings revealed a molecular link between del(5q) MDS and congenital bone marrow syndromes such as Diamond Blackfan anemia. The Ebert laboratory has also definied sets of mutations in MDS that are associated with various disease phenotypes, including overall survival and response to specific therapies.
The Ebert laboratory characterized the mechanism of action of a powerful cancer drug, lenalidomide. Lenalidomide and related compounds act through a novel mechanism, promoting the ubiquitination and degradation of specific proteins. His laboratory is also working towards the development of novel therapies for hematologic malignancies and sickle cell disease.
Kronke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinka T, Heckl D, Comer E, Li X, Ciarlo C, Hartman E, Munshi N, Schenone M, Schreiber SL, Carr SA, Ebert BL. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 2014; 343: 301-5.
Miller PG, Al-Shahrour F, Hartwell KA, Chu LP, Jaras M, Puram RV, Puissant A, Callahan KP, Ashton J, McConkey ME, Poveromo LP, Cowley GS, Kharas MG, Labelle M, Shterental S, Fujisaki J, Silberstein L, Alexe G, Al-Hajj MA, Shelton CA, Armstrong SA, Root DE, Scadden DT, Hynes RO, Mukherjee S, Stegmaier K, Jordan CT, Ebert BL. In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 2013; 24: 45-58.
Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian HM, Raza A, Levine R, Neuberg D, Ebert BL. The Clinical Impact of Point Mutations in Myelodysplastic Syndromes. New England Journal of Medicine. 2011; 364: 2496-506.
Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME, Habib N, Yosef N, Chang CY, Shay T, Frampton GM, Drake AC, Leskov I, Nilsson B, Preffer F, Dombkowski D, Evans JW, Liefield T, Smutko JS, Chen J, Friedman N, Young RA, Golub TR, Regev A, Ebert BL. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 2011; 144: 296-309.