SEP 24, 2014 2:00 PM PDT

Targeting Lysine Acetylation in Cancer

Speaker
  • Instructor in Medicine, Hematologic Neoplasia/Malignancies, Dana Farber Cancer Institute
    Biography
      Dr. Bradner received his MD from The University of Chicago in 1999. He completed his postgraduate training in Internal Medicine at Brigham and Women's Hospital, followed by a fellowship in Medical Oncology and Hematology at Dana-Farber Cancer Institute and Brigham and Women's Hospital. In 2005, he joined Dana-Farber and is currently a member of the Hematologic Malignancies staff.

    Abstract

    Master regulatory transcription factors localize to the genome in a manner influenced by chromatin accessibility and influencing global chromatin structure. With an interest in understanding chromatin-dependent signal transduction to RNA polymerase in developmental and disease biology, we have undertaken to discover and optimize small molecule modulators of chromatin regulatory factors. These incisive chemical probes have availed new insights into chromatin structure and function, and suggest plausible translational opportunities for the targeted development of drug-like derivatives in cancer and non-malignant indications. Genomewide studies of the effects of chromatin-targeting probes has revealed new structural features of the regulatory human epigenome. Using novel biotechnologies and computational approaches, we can characterize for the first time how and where chromatin-directed drugs interact with the genome. Discussed in this lecture will be mechanistic and translational efforts to modulate gene regulatory pathways of lysine acetylation in cancer transcriptional signaling. Illustrations of how this research has translated to human clinical investigation will be provided, highlighting three first-in-class drug molecules.


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