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2002 Scientific Report

  • Text
  • Institute
  • Report
  • Tumors
  • Protein
  • Signaling
  • Michigan
  • Molecular
  • Proteins
  • Laboratory

Director’s

Director’s Introduction I began writing this introduction during our 4 th annual scientific retreat, held at a lodge in the quiet beauty of upper Michigan, where all of our scientists presented overviews of their George F. Vande Woude research and their future plans. Such a retreat is intense but extremely valuable, because it provides a forum for promoting collaborations and for testing hypotheses before a lively audience. I am pleased with the progress that the Van Andel Research Institute (VARI) has made in a very short period of time on so many fronts. Some of the highlights of the past year are quite impressive to me, and I hope you will find them to be also. Each year we select a member of the scientific community to receive the Daniel Nathans Memorial Award, choosing a scientist who has emulated Dr. Nathans’ extraordinary contributions and special character. Our most recent recipient was Dr. Francis Collins, who received the award for leading this nation’s effort in determining the sequence of the human genome. His two lectures in Grand Rapids on October 2, 2001—one to the scientific/medical community and one to the general public—were exciting and visionary (see page 65). We are delighted to have recruited Eric Xu, who came to us from GlaxoSmithKline to head our Laboratory of Structural Sciences. Eric is a superb crystallographer whose work has focused on the crystal structures of nuclear hormone receptors; at our Institute, he will continue studying the structural basis for protein/DNA interactions, protein/ligand interactions, and multiprotein complexes. Our success in attracting Eric to VARI was leveraged by funding from the Michigan Life Sciences Corridor (MLSC) for the Michigan Center for Structural Biology (MCSB), which will build and operate a state-ofthe-art synchrotron beamline at Argonne National Laboratory. This technology has revolutionized our ability to solve the structure of macromolecules, proteins, and nucleic acids, and having access to this technology was instrumental in our efforts to recruit Eric. The members of the MCSB (VARI, University of Michigan, Michigan State University, and Wayne State University) partnered with Northwestern University to secure the beamline. We also were successful in recruiting Greg Cavey to establish our proteomics core facility. Greg comes with glowing credentials, having been responsible for establishing a proteomics core at Pharmacia in Kalamazoo, Michigan. The proteomics core will provide us with powerful tools necessary for measuring infinitesimal quantities of protein that contribute to cancer. At this writing, we are eagerly awaiting the arrival of our mass spectrometer, and Greg already has a backlog of samples to work with once the equipment is in place. We are grateful to Jack and Nancy Batts of Grand Rapids for endowing this laboratory through a Charitable Remainder Trust, and also to the Wege Foundation for their gift. We are pleased to announce the recruitment of David Nadziejka, our science editor. David has 22 years of experience in science editing and writing, including eight years as the lead technical editor for biology and biomedical science at Argonne National Laboratory. Since 1996, David has been the recipient of three of the four national awards given in the field of technical communication. He will be a valuable asset to our investigators as they prepare grant proposals, manuscripts, site visit reports, and other scientific documents. We have continued to expand our archive tissue repository and to establish tissue acquisition agreements with area hospitals. We have established agreements with Spectrum Health (Grand Rapids), Pennock Health Services and Hastings Surgeons P.C. (Hastings), Hackley Hospital (Muskegon), Ferguson Clinic (formerly Ferguson Hospital; Grand Rapids), and Holland Community Hospital (Holland). We are working on agreements with St. Mary’s Mercy Medical Center (Grand Rapids), and Metropolitan Hospital (Grand Rapids). Jim Resau, Rick Hay, Craig Webb, Bin Teh, and Brian Haab have worked out the methodology and conditions for collecting, storing, and processing specimens for gene expression profiling (microarray analysis) 3

and proteomics analyses. These investigators, together with Kyle Furge and Bryon Campbell’s team, generated the bioinformatics software of relational databases needed for processing, comparing, and annotating the clinical and molecular information. Collectively, we are establishing a network for translation of this research into clinical application. Our collaborations with surgeons, oncologists, and pathologists in a community hospital setting are unique and will become a powerful asset to Western Michigan. We have upgraded our imaging facility with the purchase of a multiphoton microscope. This microscope has a special detector that will enable us to see fluorescently labeled cells deep within living tissues without introducing the damage usually associated with ultraviolet light. This will enable us to not only see cells and tissues, but to follow their biology over time (as they grow, migrate, and develop) and to quantify the changes. We also are developing a state-of-theart Acusome ultrasound facility for in vivo imaging of mouse development, as well as of tumor growth and metastases using molecular markers and newly developed image-contrast reagents. Bart Williams led an effort to purchase an instrument that allows us to quickly determine bone mineral density and body fat content in living mice. This machine, obtained from GE Lunar, will be valuable in examining mutant mice that are susceptible to osteoporosis and diabetes, as well as in determining how mouse models of human cancer respond to various treatments. In June 2002, the Michigan Economic Development Corporation announced plans to fund 18 of the 111 full proposals submitted for the FY2002 competition. These projects, designed to advance the research and commercialization of cutting-edge life sciences products, represent a million commitment from the MLSC Fund. A multi-institutional collaboration to develop new approaches for imaging and treating prostate cancer, using the molecule Met as a diagnostic and therapeutic target, was funded by the MLSC for a three-year project. This effort involves three institutions within Michigan (VARI, MSU, and the Veterans Affairs Health Care System in Ann Arbor) and two in Washington State (Fred Hutchinson Cancer Research Center and the Gerald P. Murphy Cancer Foundation). VARI investigators on the grant are myself, Rick Hay, James Resau, and Brian Cao. VARI will also receive funding for the core services it provides as part of the Core Technology Alliance (CTA; comprising VARI, the University of Michigan, Michigan State University, and Wayne State University). The CTA is important to Michigan’s research efforts in that it provides cutting-edge biomedical technology services in proteomics, genomics, bioinformatics, structural biology, and animal models to all scientists in the state. Given sufficient time, this will propel Michigan into a leadership role in biotechnology. Pam Swiatek from our Institute has been a leader in helping to establish the CTA cores and is director of the Animal Models Consortium in Michigan. With Drs. Brian Ross and Alnawaz Rehemtulla at the University of Michigan, we have received an In Vivo Cellular Molecular Imaging Center (ICMIC) P50 grant for in vivo imaging of oncogene activities and metastases. This grant was awarded by the National Cancer Institute (NCI). VARI investigators on the grant are myself, Ilan and Galia Tsarfaty, Pam Swiatek, Bryn Eagleson, and Jim Resau. Ilan, a cancer biologist, and Galia, a radiologist, are visiting scientists from Tel Aviv University and the Chaim Sheba Medical Center, respectively; they have a major interest in imaging and were key to our success in obtaining this grant. We are making a significant commitment to the molecular imaging of cancer cells and tumors in animal models as a means to create a knowledge bridge between basic science and the clinical diagnosis and therapy of human pathological states. Craig Webb and Brian Haab have begun a collaborative research project with Dr. Anthony Schaeffer, chairman of the Department of Urology at Northwestern University. They will examine, by gene expression analysis and proteomics, prostatic fluids and tissue specimens from patients with various diseases of the prostate, including prostatitis, benign prostate hyperplasia, and prostate carcinoma. They will perform gene and protein profiling on these samples for different pathological states to identify useful clinical markers. Further, Brian Haab has established a collaboration with Dr. Jose Costa, director of anatomical pathology of the Yale School of Medicine, to identify markers in pancreatic cancer; the work is funded through NCI’s Early Detection Research Network (EDRN). 4

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