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2007 Annual Report

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VARI 2007 Lab Highlights VARI researchers had numerous findings published in scientific journals in 2007; an overview of some of the highlights is presented on the following pages. As you can see, we continue to gain insight into the inner workings of cells and what happens in disease, which has an impact on diagnosis, treatment, and ultimately the lives of patients. * Primary labs and journals are listed in parentheses. MET: Colon Cancer, Diagnosis, Drug Potential >> The amount of MET protein in normal tissue, benign growths, and tumors from the colon is similar, but different in varying tumor grades. This suggests that other factors triggered by MET in the cell may have a larger role in colon cancer development than MET itself. (Resau Lab - International Journal of Oncology) >> A peptide called Met-pep1 specifically interacts with Met proteins; this peptide could be used to diagnose tumors with high Met levels essentially by “tagging” Met in cells. (Cao Lab - Clinical Cancer Research) >> Mutated NK1 protein binds to cell receptors that Met protein normally attaches to, essentially blocking Met without producing its own effect in the cell. This finding could be important to the development of anti-Met cancer drugs. (Xu Lab - Proceedings of the National Academy of Sciences U.S.A.) - - VARI Director Dr. George Vande Woude discovered and characterized the MET gene, which results in the MET protein that is found in higher than normal levels in many types of cancer. MET has become a leading anti-cancer drug target. >> The Drf1 gene may play a role in myeloproliferative disease (MPD) and myelodysplastic syndrome (MDS). (Alberts Lab - Cancer Research and the Journal of Biological Chemistry) “Ultimately, our goal is to establish and use genetic models of MDS and MPD to test, evaluate, and improve upon current therapies for the disease.” —Art Alberts, Ph.D., Senior Scientific Investigator Van Andel Research Institute

Important Genes and Proteins in Cancer: Beta-Catenin, Myc, MIG-6 >> Prostate cells lacking the gene Apc multiply to form tumors and contain high levels of beta-catenin protein, suggesting that beta-catenin may play a role in prostate cancer development. (Williams Lab - Cancer Research) >> Myc protein is activated through a series of signals in the cell and associated with the aggressiveness of papillary type 2 renal cell carcinoma (RCC); blocking this signaling pathway at some point is a potential avenue for therapy. (Furge and Teh Labs - Cancer Research) >> A new method to identify alterations of carbohydrates on certain proteins in disease may be used as a means to detect or diagnose pancreatic cancer. (Haab Lab - Nature Methods) “The application of this method could lead to the discovery and characterization of carbohydrate structures that are instrumental in the pathology of cancer and other diseases. This is a first and important step in better diagnosis and treatment.” —Brian Haab, Ph.D., Senior Scientific Investigator >> Mutations in a potential tumor-suppressor gene, MIG-6, may be associated with lung cancer. (Vande Woude Labs - Oncogene) - - A tumor suppressor gene naturally helps to inhibit cancer in some way. Anthrax Insights and Use as Cancer Treatment >> The LRP6 protein, previously believed to mediate anthrax toxin’s entry into cells and thus its lethal effect, is not needed in this process. (Duesbery Lab - PLoS Pathogens) >> Treating Kaposi’s sarcoma, which is characterized by abnormally dense blood vessels, with anthrax lethal toxin results in reduced tumor growth most likely related to reduced blood vessel density. This suggests that lethal toxin or similar molecules could be used to treat Kaposi’s sarcoma. (Duesbery Lab - Clinical Cancer Research) - - Anthrax lethal toxin is a combination of two components of the toxin released by the bacteria that cause anthrax. On their own, each of these proteins that make up anthrax toxin is harmless, but when all three are combined, they can be deadly. VARI Lab Highlights 2007 www.vai.org 09

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