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2015 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report 2015 Ning Wu, Ph.D. Laboratory of Cancer Signaling and Metabolism Dr. Wu received her Ph.D. in the Department of Biochemistry of the University of Toronto in 2002. She then served as a research associate at the Scripps Research Institute in the Department of Chemistry. In 2004, she joined the Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School, as a research fellow in a lab studying the signaling pathways that regulate normal mammalian cell growth and the defects that cause cell transformation. Dr. Wu joined VARI in 2013 as an Assistant Professor. Research Interests Our laboratory investigates the interface between cellular metabolism and signal transduction. The generation of two daughter cells depends on the proper uptake and use of nutrients that are often limited in the tumor environment. The distribution of these nutrients is controlled not only by the intrinsic catalytic rate and allosteric regulation of the enzymes, but also by posttranslational modifications of these enzymes by signaling molecules. At the same time, signaling molecules must respond to cellular nutrient status and other cues such as environmental stresses and growth factors. Our laboratory focuses on key metabolic steps in glucose and lipid catabolism and aims to understand the mutual regulation between metabolites and signaling during cell replication. Fundamentally, cancer is a disease of uncontrolled cell growth. Relative to normal cells, tumor cells have aberrant metabolic addictions that differ depending on the cell’s tissue of origin and genetic mutations. By understanding the energy requirements and regulatory pathways of tumor cells, more-effective treatments can be developed. Our projects include unraveling the molecular mechanisms that regulate glucose uptake in cancers, investigating the effect of glucose on mitochondrial activity, and exploring the role of glucose as the link between metabolic syndrome and cancer incidence. From left: Nelson, Wu, Weston Staff Amy Nelson Students Kelsey Veldkamp Erin Weston, B.A. 38

Qian Xie, M.D., Ph.D. Molecular Oncogenesis and Targeted Therapy Dr. Xie received her M.D. from Fudan University Shanghai Medical College, China, in 1995. She then joined Fudan’s Zhongshan Hospital to study the molecular mechanisms of cancer invasion and metastasis. She received her Ph.D. degree in oncology in 2002 and then joined George Vande Woude as a postdoctoral fellow. She is now a Research Assistant Professor. Research Interests Our work focuses on the molecular mechanisms of MET drugs, and we were the first to report that HGF-autocrine activation may be a molecular feature that can predict the sensitivity of glioblastoma patients to MET inhibitors. We validated that finding in liver cancer models, in which HGF-autocrine activation is also related to MET inhibitor sensitivity. We plan to explore the opportunity to translate this finding to the clinical side. The goal of targeted therapy requires animal models that mimic the human cancer phenotype and genotype. We have invested great effort in characterizing patient-derived xenograft models of glioblastoma that show invasive tumor growth and in developing human-HGF transgenic mice that produce spontaneous hepatocellular carcinomas having genomic profiles similar to those of the human disease. Real-time imaging procedures have been established to monitor tumor growth. From these studies, we have learned key principles for establishing and optimizing preclinical models for targeted therapy. Recent Publication Xie, Qian, Yanli Su, Karl Dykema, Jennifer Johnson, Julie Koeman, Valeria De Giorgi, Alan Huang, Robert Schlegel, Curt Essenburg, et al. 2013. Overexpression of HGF promotes HBV-induced hepatocellular carcinoma progression and is an effective indicator for Met-targeting therapy. Genes & Cancer 4(7-8): 247–260. From left: Kang, Johnson, Xie Staff Jennifer Johnson, M.S. Liang Kang, A.S. 39

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