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2007 Scientific Report

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VARI |

VARI | 2007 In addition, four of VARI’s original investigators have been promoted to the rank of Senior Scientific Investigator: Art Alberts, Brian Cao, Nick Duesbery, and Bart Williams. Art’s studies on Diaphanous-related formins and the DAD peptide have developed new insights into the assembly of cell structures and the possibility of new approaches to cancer therapy. He has recently played a key role in establishing VARI’s flow cytometry facility. Brian Cao was recognized for the development of VARI’s state-of-the-art antibody technology lab. He has produced novel antibodies for several VARI research programs, developed and improved his lab’s capabilities to meet research needs, and further serves as director of the Michigan Antibody Technology Core of the Core Technology Alliance. Nick Duesbery’s work with anthrax lethal toxin has shown that the lethal factor component of the toxin is a metalloprotease that cleaves MAPK kinases. His lab’s work has increased our understanding of how anthrax toxin works and has also shown that the two-component moiety called “lethal toxin” inhibits the growth of some tumors. In addition to directing his lab, Nick also serves as VARI’s Deputy Director for Research Operations. Bart Williams has pursued the regulation and function of Wnt signaling as it affects various key cellular processes. The breadth of Wnt’s effects has led him from an initial interest in Wnt’s effects in tumorigenesis to the recognition of the role of Wnt in bone development and disease. Bart has also been a major contributor to the development of VARI’s mouse models and to the inception of the VAI graduate school. 3 We congratulate each of these researchers, and we look forward to their continued valuable contributions toward the Institute’s goals. We are pleased to announce the recruitment in 2006 of two exceptional principal investigators (PIs). Jeff MacKeigan, Ph.D., was recruited from Novartis and has established the Laboratory of Systems Biology. Jeff is interested in phosphatases and kinases, how they are regulated, and what signaling pathways they affect. He also brings platform screening technology to our program and has stimulated collaborations with our PIs to use RNAi screens as a genetic tool to understand gene function. Steve Triezenberg, Ph.D., was recruited from MSU and he wears two hats. In addition to Steve’s studies of herpes virus transcription in his newly established Laboratory of Transcriptional Regulation, he is also founding Dean of our new graduate program, established by VAEI. To Steve’s great credit, VAEI’s graduate school has an inaugural class of students that will arrive to begin studies in August 2007. The Ph.D. program, like most of the research at VARI, will focus on the molecular, cellular, and genetic biology of human disease with a pronounced emphasis on translational research. The graduate school will foster the effective transition of students into professional scientists through a unique curriculum employing problem-based learning methods and through workshops to develop the cognate skills of grant and manuscript preparation, financial management, small-group leadership, and career planning. Programs On June 1, 2006, the Program for Translational Medicine was established under Craig Webb’s direction. This program will push forward our emphasis on moving our research findings into clinical practice and will help to develop “personalized medicine” founded on molecular-based, individual diagnosis and treatment. Craig’s staff will be developing strategies for data collection, integration, and analysis using the XB-BioIntegration Suite (formerly Xenobase), and Craig will work closely with the Office of Translational Programs, directed by Rick Hay, to help achieve VARI’s translational aims.

Van Andel Research Institute | Scientific Report The Institute’s entire animal care and use program was evaluated in March 2007 by the Association of Assessment and Accreditation of Laboratory Animal Care, as part of our application for accreditation. AAALAC standards go beyond governmental regulations, and meeting their standards symbolizes quality, promotes scientific validity, demonstrates accountability, and shows commitment to humane animal care. The preliminary results of the review were very favorable, and we anticipate receiving approval and our formal accreditation in a timely manner. Our thanks to Pam Swiatek and Bryn Eagleson and their staffs, as well as to all the others involved in preparing for this evaluation; they did a great job in getting us ready. Grants In 2006, Eric Xu received his second R01 from NIH for a five-year study of “Structure and Function of Steroid Hormone Receptors”. Also, Brian Haab received his second R21 grant for “Defining Secreted Glycan Alterations in Pancreatic Cancer”. Rick Hay received a state appropriation from the MEDC Michigan Strategic Fund for “Creation of a Good Manufacturing Practices (GMP) Facility”. The project support runs from October 2006 through December 2007. Steve Triezenberg’s graduate student, Sebla Kutluay, received VARI’s first predoctoral grant, for two years from the American Heart Association. Sponsored funding by commercial firms for specific research areas was received by the laboratory of Bin Teh and by my own lab. Other funding was received by various labs from the Breast Cancer Research Foundation, American Cancer Society, and as subgrants through collaborations with other research organizations. 4 Collaborations In late 2006, we established a collaboration for medical education and research between MSU and VARI. The new CHM medical school will establish an innovative molecular medicine curriculum with research in areas including cancer and neurobiology and an emphasis on translational research. The medical school faculty will have laboratory space in our Phase II building upon its completion in 2009, and the school intends to be fully operational in 2010. We anticipate that unique and fruitful collaborations will result from the proximity of the MSU and VARI scientists, and we foresee benefits accruing not only to both institutions, but more importantly to the patients afflicted by the diseases we study. Also in 2006, our joint effort with Spectrum Health has created the Center for Molecular Medicine, which offers molecular-based diagnostics to physicians. Further, a multi-member alliance under the name “ClinXus” offers a venue for novel biomarker-based clinical trials and for future biomarker drug development collaborations with pharmaceutical and biotech firms. In February 2007, we signed a groundbreaking agreement with the National Cancer Center, Singapore (NCCS) to establish a joint translational research program in Singapore. The program will be directed by Bin Teh and will focus on the biological basis for different drug responses in Asian versus non-Asian patients having specific cancers. When we opened our doors in 2000, our commitment to basic sciences and translation was considered new and innovative. Lately, as I travel to other world-class academic institutions, it is clear that everyone has the same burning desire to turn discovery into application. This means that our success will be contingent not only on having the right scientific expertise, but also upon the growth of an ideal medical environment and a very supportive community. I know Grand Rapids has the “right stuff” and is poised to become a leading biomedical center in the next decade. It is an honor to be a part of such an exciting endeavor.

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