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Dr. Ali Shilatifard Stowers Institute, USA2 Lectures 1 Series
Dr. Ali Shilatifard is a biochemist/molecular biologist with an immense interest in understanding the molecular mechanism of the regulation of gene expression. As a Jane Coffin Childs postdoctoral fellow, Shilatifard made a seminal contribution to the field of leukemia biology by identifying the first function of any of the MLL... read moretranslocation partners. Shilatifard identified ELL as a RNA Polymerase II (Pol II) elongation factor. Since its inception in 1997, the central theme in the Shilatifard’s laboratory has been the identification of the molecular properties of both MLL and ELL and why their translocations result in leukemogenesis. As a result, Shilatifard’s laboratory demonstrated that many of the MLL partners in leukemia are found with ELL within the Super Elongation Complex (SEC) regulating the transcription of the MLL-chimera target genes. In addition to his studies on ELL, within the past 15 years, Shilatifard's laboratory identified the yeast homologue of MLL, the Set1 protein in a complex named COMPASS, as the first histone H3K4 methylase. Based on these fundamental yeast studies, we now know that MLL is also found in a COMPASS-like complex functioning as an H3K4 methylase. Shilatifard’s lab has demonstrated that there are three COMPASS family member in Drosophila and six COMPASS family members in mammalian cells with distinct catalytic functions. Recent studies from his laboratory identified Drosophila Trr and mammalian MLL3/MLL4/COMPASS family members as enhancer histone H3K4 monomethyltransferases functioning in enhancer-promoter communication. Recent genome-wide studies in the cataloging of somatic mutations in cancer have identified mutations in intergenic sequences encoding regulatory elements, and in MLL3 and MLL4 in both hematological malignancies and solid tumors. Shilatifard’s laboratory has proposed that cancer-associated mutations in MLL3 and MLL4 exert their properties through the malfunction of Trr/MLL3/MLL4-dependent enhancers.