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.
Puram RV, Kowalczyk MS, de Boer CG, Schneider RK, Miller PG, McConkey M, Tothova Z, Tejero H, Heckl D, Järås M, Chen MC, Li H, Tamayo A, Cowley GS, Rozenblatt-Rosen O, Al-Shahrour F, Regev A, Ebert BL. Core circadian clock genes regulate leukemia stem cells in AML. Cell, 2016; 165: 303-16.
Kronke J, Fink EC, Hollenbach PW, MacBeth KJ, Hurst SN, Udeshi ND, Chamberlain PP, Mani DR, Man HW, Gandhi AK, Svinkina T, Schneider RK, McConkey M, Jaeras M, Griffiths E, Wetzler M, Bullinger L, Cathers BE, Carr SA, Chopra R, Ebert BL. Lenalidomide induces ubiquitination and degradation of CK1a in del(5q) MDS. Nature, 2015, 523: 183-8.
Jaiswal S., Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins, JM Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI on behalf of T2D-GENES, Boehnke M on behalf of GoT2D, Altshuler D on behalf of SIGMA T2D, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL. Age-related clonal hematopoiesis associated with adverse outcomes. New England Journal of Medicine 2014, 371(26):2488-98.
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.