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TUESDAY, OCTOBER 2

7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

Exploring Novel Strategies

8:15 Chairperson’s Opening Remarks

Matthew D. Petroski, Ph.D., Assistant Professor, Sanford-Burnham Medical Research Institute

8:20 Selected Oral Poster Presentations:

     1) TRIM3, an E3 Ligase forOncogenic p21 [Cip1/Waf1] in Gliomas

         Radhika R. Suresh, Cornell University

     2) The Ubiquitin Protease UBP43 is an Antineoplastic Target

         Fadzai Chinyengetere, Dartmouth Medical School

8:50 Development of a Novel Selective Inhibitor of Posh for the Potential Treatment of Cancer and Inflammatory Diseases

Philippe Nakache, Ph.D., Head, Chemistry, Proteologics, Ltd.

The presentation will describe the development of a new inhibitor of POSH and describe the results available so far in in vitro and in vivo studies.

9:20 A Novel Bacterial Genetic System to Identify New Targets and Leading Drugs of the Ubiquitin Pathways

Gali Prag, Ph.D., Principal Investigator, Department of Biochemistry and Molecular Biology and the Institute for Structural Biology, Tel Aviv University, Israel

The action of deubiquitylating enzymes, and the immense number of E3-ligases and substrates, all pose challenges to assign particular substrates to specific E3s. To circumvent this limitation we developed a reconstituted genetic system for ubiquitylation in E.coli. In-frame tethering a split reporter gene onto the ubiquitylation cascade facilitates the screening of selected components. The use of the system for identification of new targets and leading drugs discovery will be demonstrated.  

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

10:40 Ubiquitin Pathway-Related Target Finding in the Context of Wnt

Feng Cong, Ph.D., Scientist, Novartis

Perturbation of Wnt signaling can lead to degenerative diseases and tumorigenesis, while agents that restore balance to Wnt signaling pathway output are predicted to have therapeutic value in such disease states. Using genetic and chemical genetic screens, we have identified tractable targets of the ubiquitin system that regulate the stability of Axin and Frizzled, two core components of the Wnt pathway. Molecular characterization and therapeutic exploration of these regulatory mechanisms will be discussed.

11:10 Deubiquitinating Enzymes as Drug Targets in Cancer

Sebastian Nijman, Ph.D., Principal Investigator, Chemical Genomics, The Research Center for Molecular Medicine, Vienna, Austria

Targeting enzymes involved in the ubiquitin machinery is receiving increasing attention as a strategy to treat cancer. We have recently found that the Ubiquitin protease USP4 regulates the master kinase PDK1 and have developed screening strategies to identify cancer cell vulnerabilities involving other deubiquitinases. In addition, I will present a novel technology to perform human test tube to discover drug targets, including the generation of a genome-wide collection of knockout cells.

11:40 Cancer Cell Resistance to the NEDD8-Activating Enzyme Inhibitor MLN4924

Matthew D. Petroski, Ph.D., Assistant Professor, Sanford-Burnham Medical Research Institute

MLN4924, developed by Millennium Pharmaceuticals, is a first generation NAE inhibitor in clinical development for hematological and advanced non-hematological malignancies. Using an in vitro cancer cell selection strategy, we have discovered on-target mutations that decrease sensitivity to the molecule. I will describe our characterization of MLN4924 resistance mechanisms and discuss the implications on NAE and other activating enzymes as therapeutic targets.

12:10 pm Close of Conference

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