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2005 Scientific Report

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Director’s Introduction We are now in our fifth year since the opening of the Van Andel Institute. The Institute was created because of the generosity of Jay Van Andel and his wife Betty, both of whom George F. Vande Woude passed away in 2004. While deeply saddened by their loss, we continue our endeavor to fulfill their vision of a center for research and education excellence in the heart of Grand Rapids. I know Jay was able to see the beginning of what a great contribution he made to society and the betterment of human health. Sharing his and Betty’s vision, we have begun to expand our research beyond cancer biology into the field of neurological disorders. David and Carol Van Andel, in Jay’s honor, have created an endowed chair dedicated to Parkinson disease (PD) research. The search for a leading scientist to take this chair is now underway. Already, Jim Resau and Bin Teh have initiated a collaboration with Australian scientists Alan Mackay-Sim and Peter Silburn at Queensland University in Australia to better understand Parkinson disease and how it develops. Alan is a developmental biologist who has initiated some exciting discoveries using adult olfactory stem cells. Peter is a neurologist who studies and treats PD patients. Together with these new collaborators, we will increase our understanding of the function, growth, and death of human nerve cells as models for PD. In addition, these approaches will be used in the study of Alzheimer disease pathophysiology. Our scientists have also partnered with the St. Mary’s Hauenstein Parkinson Center—named in honor of lead donor (and VAI trustee) Ralph Hauenstein—to determine the interactions of the environment and genes associated with PD. We will learn how these genes correlate with disease progression and drug response. We are pleased to announce that, in collaboration with the Van Andel Education Institute, the Research Institute is developing a graduate school with a program leading to the Ph.D. degree in cellular and molecular genetics, with an emphasis on translation. We expect the graduate program to contribute to the vitality and creativity of our successful research programs and to also address the nation’s need for expertise in the life sciences and biotechnology. We have received a charter from the state of Michigan and have appointed a Board of Directors for the school. Our goal is to have our first students on board in September 2006. Personnel A special occasion occurred this past year with our first promotion review. We are very proud to announce the promotion of Bin Tean Teh to Distinguished Scientific Investigator, our highest appointment level. Bin has made major contributions to the understanding of kidney, nasopharyngeal, and endocrine cancer. In recognition of his efforts, Bin was recently appointed to the Medical Advisory Board of the Kidney Cancer Association. We are also proud to announce the appointment of Rick Hay as a Senior Scientific Investigator. Rick will establish the Laboratory of Animal Imaging. Our congratulations to both scientists! Sara Courtneidge has taken a position at the Burnham Institute and is relocating her laboratory in early summer 2005. Sara and I have been friends and colleagues for over 20 years. I was delighted when she joined VARI and I am grateful for all her contributions to the Institute, especially her efforts in helping to establish the graduate program with MSU and the VARI postdoctoral advisory committee. The Burnham Institute is very fortunate to have recruited her, where she will be reunited with her many West Coast friends. I am sorry to see her leave, but I wish her great success and look forward to our continued scientific interactions. Publications and Competitive Funding As of April 1, 2005, there have been 190 peer-reviewed articles published by VARI investigators. In December 2004, a VARI article was featured on the cover of the Journal of Bone 3

and Mineral Research; in January 2005, we had a featured article in Molecular Cell; and in February, a VARI article in Cancer Cell was the source of the issue’s cover photo. Our investigators have also demonstrated their competitive research abilities in terms of receiving grants for funding of their work. In fiscal year 2004, extramural funding for VARI dramatically increased over that in 2003. Seventeen of our scientists and six of our postdoctoral fellows received funding from 42 grants. Our new major awards have come from a variety of sources. The National Institutes of Health (NIH) National Cancer Institute (NCI) made two awards to Nick Duesbery. The first was an R01 grant for studying MEK signaling in sarcoma growth and vascularization. The second grant, an R21, was for investigating the antitumor effects of an anthrax toxin moiety (which we have termed tumor lethal factor, or “TLF”) on Kaposi sarcoma. Nick’s lab has been developing TLF as a potential cancer therapeutic. Brian Haab was awarded an R21 NCI grant for a two-year project entitled “Longitudinal Cancer- Specific Serum Protein Signatures.” This project seeks to develop protein microarray methods for detecting and diagnosing prostate cancer by examining changes over time in several cancerrelated proteins in serum. And, Art Alberts received an R21 award from the NIH to exploit a discovery in his lab with a long-term goal of developing novel anti-cancer therapies. The American Cancer Society awarded two Research Scholar Grants to our researchers. One grant, to Art Alberts, is for a four-year project to study Diaphanous-related formins in myelodysplasia. Art has been studying the role of formins in cancer. A second American Cancer Society grant was awarded to Michael Weinreich. Michael is identifying small-molecule inhibitors of Cdc7 kinase for study of its regulation in DNA replication, with a long-term goal of identifying novel targets for cancer diagnosis and therapy. Two major grants have also been received from the Michigan Technology Tri-Corridor (MTTC). One award went to Rick Hay for the development of novel agents for nuclear imaging and therapy of Met-expressing human tumors. The project is a collaboration among scientists at VARI, Michigan State University, the Department of Veterans Affairs Healthcare System in Ann Arbor, ApoLife, Inc., and the National Cancer Institute. A second grant was awarded to Bin Teh for the development of the “RenoChip,” a diagnostic and prognostic tool for use against kidney cancer. In addition, the Department of Defense awarded Eric Xu a grant for a three-year study of the structure and function of the androgen receptor in prostate cancer. Eric’s lab aims to make progress in understanding the androgen dependence (or independence) of prostate cancer. Funding from other sources in the past year has included Brian Haab’s grant from DHHS/ NCI via the University of Michigan for a project entitled “Accelerated Cancer Biomarker Discovery.” This project is being undertaken by a consortium of laboratories and focuses on the development and application of new proteomics technologies for cancer biomarker discovery. Bin Teh has received a grant from the Schregardus Family Foundation for a project on renal cell carcinoma (RCC) in which his lab will be studying the prognostic value of genes for improving the clinical management of RCC patients. Bin is also the recipient of a grant from the Gerber Foundation for gene expression profiling in newborns with congenital chromosomal abnormalities. We are also proud that three of our postdoctoral fellows have received awards. Carrie Graveel (Vande Woude lab) and Kate Eisenmann (Alberts lab) have received National Research Service Awards from the NIH, while Jennifer Bromberg-White (Webb lab) received a fellowship award from the Multiple Myeloma Research Foundation. Looking to the Future We now look to expanding not only our research goals but the Institute itself. On May 17th we celebrated our fifth anniversary, and our CEO, David Van Andel, announced that in 2006 we will begin the second construction phase of our Institute. The new building, a model of which is displayed in the Cook-Hauenstein Hall, will join and mirror our current exceptional facility, but it will provide two-and-a-half times the existing laboratory space, or an additional 150,000 square feet. 4

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