WIM no. 17 Spring 2020

מכון ויצמן למדע recycling of these metabolites. More specifically, they determined that urea cycle enzymes and related changes in metabolites can potentially serve as biomarkers for early detection of cancer, and may be used to determine whether individual patients will respond well to cancer immunotherapy. Drugs targeting a cancer-causing genetic mutation: Dr. Nir London’s lab in the Department of Organic Chemistry designs cancer drugs that target specific mutations in tumor cells in a personalized manner. One focus is a specific mutation in the p53 gene—the most frequently mutated gene in cancer—called R273C, which leads to the development of tumors. Dr. London's group identified the first-ever molecules that can strongly and specifically bind to p53 harboring this mutation, and are working to translate this binding to cause regression of the tumor. Such compounds could serve as drug candidates in the future, for the hundreds of thousands of patients with this mutation. Proteins that drive and inhibit cancer: Dr. Yifat Merbl in the Department of Immunology focuses on the regulation of proteins in cancer and immunity. Maintaining protein homeostasis involves an extensive protein network of more than 1,000 proteins that are responsible for sensing and responding to cellular stress, to allow proper function. Her lab investigates both how proteins are regulated and modified—so-called post-translational modifications—and how they are degraded in health and disease. The lab has developed novel technologies to profile the protein modification and degradation landscape in clinical samples. Among other findings, Dr. Merbl has found a particular modifying protein called FAT10 that regulates the infiltration of tumors into the immune system’s T cells; inhibiting this protein could potentially refine immunotherapy techniques. She is investigating this and other “control mechanisms” that proteins undergo in the cell, which may affect tumor progression and the response to therapy. and detection and towards improving patient outcomes. The foundation is also keen on boosting the “multiplier effect” referred to by Mr. Zellmayer, by inspiring other philanthropists and agencies to support the same projects—and thereby help move them forward at an even more rapid pace. While the first funding stage was successful, the next stage “could have an even greater impact,” says Zellmayer. Mr. Stephenson’s reasoning for supporting translational cancer research always goes back to the patient, and what he calls “the ‘Mother Standard of Care’ (a trademarked phrase) that is the hallmark of their operations in the US and Europe. “We want to be able to offer cancer patients everything we’d want to be able to offer our own mothers if they were sick…We want to empower patients by being able to offer themmore options—to enlarge the number of choices they have. This is why we invest in translational cancer research. We are very pleased with our relationship with Weizmann and we are looking forward to intensifying it.” g Dr. Yifat Merbl “We want to empower patients by being able to offer them more options… This is why we invest in translational cancer research,” says Shawn Stephenson. Weizmann MAGAZINE 30–31 S P R I N G 2 0 2 0