Protein Homeostasis, Metabolism, and Cancer:
Major advances in biomedical research are being made in understanding disease mechanisms from the point of view of the genome, the metabolome and the proteome. The 2014 Vallee Symposium, held at the Mandarin Oriental Hotel in Boston earlier this month, was organized by Peter Howley (VVP 2009), Wade Harper (VVP 2000), and Lew Cantley (VVP 2006). It brought together 16 world-renowned scientists working in related areas to present their newest work.
Ivan Dikic (VPP 2014; Goethe University Medical School), Ana Maria Cuervo (Albert Einstein College of Medicine), Jennifer Lippincott-Schwartz (Eunice Kennedy Schriver National Institute of Child Health & Human Development), and Richard Youle (National Institute of Neurological Diseases & Stroke) discussed mechanisms of protein quality control by a process called autophagy (self-eating). This discussion was complemented by talks from Franz-Ulrich Hartl (Max Planck Institute of Biochemistry) and Jeff Kelly (The Scripps Research Institute) on protein folding and protein quality control regulatory systems in cells.
Ubiquitin is a major pathway controlling protein abundance in cells. Kylie Walters (National Cancer Institute) and Brenda Schulman (St Jude Children’s Research Hospital) presented new studies on the molecular architecture of machines (ubiquitin ligases and the proteasome) that control the turnover of a large fraction of the proteome, while the use of ubiquitin to control immune signaling pathways was described by Phil Cohen (VVP 2013; University of Dundee). Chris Claiborne (Takeda Pharmaceuticals International Co) described approaches for drugging both the ubiquitin system and autophagy for cancer therapy.
The p53 tumor suppressor gene is one of the most frequently mutated genes in human cancer and is one of the most widely studied genes in biology. Arnold Levine (VVP 2013; Institute for Advanced Study) and Karen Vousden (Beatson Institute of Cancer Research) discussed the complex genetics and biochemistry of the p53 tumor suppressor. Finally, Nick Tonks (VVP 2012; Cold Spring Harbor Laboratory), Lew Cantley (VVP 2006, Weill Cornell Medical College & New York-Presbyterian Hospital), Craig Thompson (Memorial Sloane Kettering Cancer Center), and David Sabatini (Massachusetts Institute of Technology) discussed new approaches for treatment of cancer that focus on the interface between oncogenic signaling and energy usage by cancer cells.
The meeting was greatly complemented by 12 Boston area academic scientists working in these areas, as well as a number of other previous VVPs and Vallee Foundation Board members, who made sure the question period was as stimulating as the presentations. The scientific program was further augmented by a group of twenty postdoctoral trainees from abroad as well as the Boston area, who presented their work in a lively poster session on the first afternoon. Finally, Kirsty Spalding (Karolinska Institutet), David Tobin (Duke University Medical Center) and Feng Zhang (Massachusetts Institute of Technology), the first three recipients of Vallee Young Investigator Awards, were introduced by the foundation president James Adelstein, and each gave a brief description of their research interests. In the tradition of the Vallee Foundation, the exciting science and thought-provoking discussions that marked the Symposium were complemented by some outstanding meals that fostered interactions among the participants.