Several lines of evidence argue for the existence of a subpopulation of quiescent leukemia stem cells (LSC) or leukemia initiating cells (LIC) that fail to be killed by chemotherapeutic agents that work best on dividing cells. Therefore, knowledge of the regulation of LSC quiescence holds great therapeutic value. Using a combination of mouse genetics and chemical genetics approaches, our lab is in a unique position to elucidate the mechanism of MECOM in LSC regulation, and to target its protein:DNA interaction, as well as its protein complex with small molecule inhibitors, and hopefully develop a series of novel and effective therapies for acute myeloid leukemia.
|
Zhang Y, Owens K, Hatem L, Glass CH, Karuppaiah K, Camargo F, Perkins AS. "Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia." Blood. 2013 Oct 17; 122(16):2888-92. Epub 2013 Sep 10. |
| Arshad M, Ye Z, Gu X, Wong CK, Liu Y, Li D, Zhou L, Zhang Y, Bay WP, Yu VC, Li P. "RNF13, a RING finger protein, mediates endoplasmic reticulum stress-induced apoptosis through the inositol-requiring enzyme (IRE1?)/c-Jun NH2-terminal kinase pathway." The Journal of biological chemistry. 2013 Mar 22; 288(12):8726-36. Epub 2013 Feb 01. |
| Glass C, Wuertzer C, Cui X, Bi Y, Davuluri R, Xiao YY, Wilson M, Owens K, Zhang Y, Perkins A. "Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia." PloS one. 2013 8(6):e67134. Epub 2013 Jun 27. |
| Zhang Y, Stehling-Sun S, Lezon-Geyda K, Juneja SC, Coillard L, Chatterjee G, Wuertzer CA, Camargo F, Perkins AS. "PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function." Blood. 2011 Oct 6; 118(14):3853-61. Epub 2011 Jun 10. |
| Zhang Y, Sicot G, Cui X, Vogel M, Wuertzer CA, Lezon-Geyda KA, Wheeler JC, Harki DA, Muzikar KA, Stolper DA, Dervan PB, Perkins AS. "Targeting a DNA binding motif of the EVI1 protein by a pyrrole-imidazole polyamide." Biochemistry. 2011 50(48):10431-41. Epub 2011 Nov 10. |