Convergence of Circadian Clock and Cancer

11th December 2017.  
Chi Van Dang, Ludwig Institute for Cancer Research, Philadelphia              

Chi Van Dang, Director of the Ludwig Institute for Cancer Research and Head of the Ludwig Institute Unit located at the Wistar Institute in Philadelphia, will give the opening lecture of the PhD Programme of the University of Pavia on Monday the 11th of December in Aula Magna (Strada Nuova) at 10.30.  The lecture, entitled Convergence of Circadian Clock and Cancer: Time as an Inconvenient Truth, will tackle a new area in cancer research that may greatly extend our understanding of the disease.  The poster of the lecture can downloaded here and all College students of Biology, Biotechnology and Medicine are strongly encouraged to attend.  Chi Van Dang will be a guest of the College during his stay in Pavia.

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kyneurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Chi Van Dang oversees the execution of Ludwig’s scientific strategy, with a special focus on the operations and staffing of the Lausanne, Oxford and San Diego Branches of the Ludwig Institute for Cancer Research. He also manages the alignment of their efforts with those of the six independent Ludwig Centers across the US to further cultivate collaboration within Ludwig’s global research community. As a researcher, Chi Van Dang is best known for his work on the molecular signaling pathways and mechanisms that govern the unusual metabolism of cancer cells, which require vast quantities of energy and molecular building blocks to sustain proliferation. Chi Van Dang's laboratory was the first to show that a master regulator of gene expression named MYC—a gene whose mutation or aberrant expression is associated with many types of cancer—alters the utilization of a key sugar in cancer cells. This body of work bolstered the hypothesis that cancer cells can become addicted to their reengineered metabolic signaling and that disrupting these pathways could be a powerful approach to treating cancer. Chi Van Dang currently leads a Ludwig laboratory housed at The Wistar Institute in Philadelphia. Prior to joining Ludwig, he served as Director of the Abramson Cancer Center at the University of Pennsylvania Perelman School of Medicine, where he launched a series of Translational Centers of Excellence to develop novel interventions for various cancers. He began his career in medicine and research at Johns Hopkins University School of Medicine, where he was Director of the Division of Hematology and eventually became the Johns Hopkins Family Professor in Oncology Research, the Vice Dean for Research and Director of the Hopkins Institute for Cell Engineering. He has authored over 250 scientific and medical articles, book chapters and two books and am a member of the National Academy of Medicine (Institute of Medicine), American Academy of Arts & Sciences and chair the National Cancer Institute’s Board of Scientific Advisors.

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