Structure and Function of Epigentic Regulators in Human Disease

Structure and Function of Epigenetic Regulators in Human Disease

Cigall Kadoch, PhD, Assistant Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School and an Institute Member of the Broad Institute of MIT and Harvard

Cigall Kadoch is an Assistant Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School and an Institute Member of the Broad Institute of MIT and Harvard. Dr. Kadoch studies chromatin regulation, with strong focus on the structure and function of the mammalian SWI/SNF or BAF family of chromatin remodeling complexes in human cancer. Her work has been centered in mechanistically interrogating rare, molecularly well-defined cancers, to understand the role these complexes play in promoting a wide range of more common cancer types.

Chris Fry, PhD, Director, Product Development at Cell Signaling Technology

Christopher Fry received his B.S. in Biology from Indiana University-Bloomington, where as an undergraduate he worked on a project utilizing mini-Tn5 transposon-mediated mutagenesis to identify novel genes regulating chemotactic responses and motility in the photosynthetic bacterium Rhodospirillum centenum. In 1999, Christopher earned his Ph.D. in Oncology from the University of Wisconsin-Madison, where he examined the mechanisms of E2F-mediated gene regulation during G1 and S phases of the mammalian cell cycle. Christopher then carried out his post-doctoral studies at the University of Massachusetts Medical School, where he studied mechanisms governing gene regulation, silencing, and chromatin dynamics during the cell cycle in the yeast Saccharomyces cerevisiae. Chris is currently an Associate Director of Product Development at Cell Signaling Technology, where he leads two teams, one that focuses on the development of antibodies against protein and non-protein targets involved in epigenetics, and the other that focuses the development of products for chromatin IP (ChIP).

Structure and Function of Epigenetic Regulators in Human Disease

Part 1 – Cigall Kadoch, Ph.D. (30 min.)

Exome- and genome-wide sequencing studies in human cancer have revealed a striking frequency of mutations in the genes encoding subunits of the mammalian SWI/SNF (BAF) family of ATP-dependent chromatin remodeling complexes. We recently determined these mutations to be broadly recurrent in over 20% of all cancers. I will present studies focused on the assembly and topological architecture of mammalian SWI/SNF complexes, cancer-specific complex subunit and associated protein factor composition, and novel approaches toward the identification of small molecule therapeutics for this class of human tumors.

Part 2 – Chris Fry, Ph.D. (30 min.)

The robustness and reliability of chromatin immunoprecipitation (ChIP) and ChIP-seq data is highly dependent on the quality of the antibodies and chromatin preparation used in the immunoprecipitation. I will provide an overview of the development and validation of new high quality recombinant rabbit monoclonal antibodies that show improved specificity, sensitivity, and reproducibility in ChIP and ChIP-seq assays. In addition, I will discuss important factors to consider for optimizing different types of target proteins, including histones, transcription factors, and transcription cofactors.

Learning Objectives:

-The assembly and biological architecture of mammalian SWI/SNF complexes..
-The role of cancer-specific SWI/SNF complex mutations (present in 20% of cancers) in driving oncogenicity.
-Novel approaches toward the identification of small molecule therapeutics for this class of human tumors.
-Development and validation of new high quality recombinant monoclonal antibodies for ChIP and ChIP-seq.
-Important factors to consider for optimizing different types of proteins – including histones, transcription factors, and cofactors – for ChIP.

SPONSORED BY: Cell Signaling Technology

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