Shilatifard is the Chairman of the Department of Biochemistry at Northwestern University Medical Center. Over 20 years ago, Shilatifard purified yeast Set1 as the MLL homologue in a complex named COMPASS, capable of methylating histone H3K4 and demonstrated that the COMPASS family is highly conserved from yeast to human. He also identified many of the MLL partners in leukemia within the Super Elongation Complex, linking leukemia to transcriptional elongation control. Shilatifard is one of the inaugural recipients of the Outstanding Investigator Award from the National Cancer Institute. He serves as a Senior Editor for the journal Science, and serves on the Scientific Advisory Boards of Genentech and the Max Planck Society.
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