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2008 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report Overall, the mDia1 knock-out phenotype resembles human chronic myeloproliferative syndrome (MPS) and myelodysplastic syndrome (MDS). Both MPS and MDS have been characterized as preleukemic states, with variable lymphopenia, excess or dysfunctional erythrocytes, chronic myelomonocytic leukemia, ineffective hematopoiesis, and, in some cases, advancing myelofibrosis. Instances of neutrophilic dermatoses (Sweet syndrome) can also accompany MDS and MPS. MDS is a frequent hematologic disorder that typically affects older patients and is thought to be a stem cell disorder. Dysplastic features of the nucleus or cytoplasm, as observed in the mDia1 knock-out mice, and altered cellularity of the bone marrow are also characteristic of MDS. The effect of Drf1 gene targeting and the resulting mDia1 knock-out suggests that the DRF1 gene for human mDia1 is affected in MPS, MDS, or other preleukemic pathologies. Ongoing studies are focused on examining if defects in the human gene encoding mDia1 might be defective in MDS patients. Recent Publications From left: Matheson, Rodriguez, West, Strunk, DeWard, Guthrey, Leali, Kitchen, Eisenmann, Alberts Uma, Kamasani, James B. DuHadaway, Arthur S. Alberts, and George C. Prendergast. In press. mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition. Cancer Biology & Therapy. Sarmiento, Corina, Weigang Wang, Athanassios Dovas, Hideki Yamaguchi, Mazen Sidani, Mirvat El-Sibai, Vera DesMarais, Holly A. Holman, Susan Kitchen, Jonathan M. Backer, Art Alberts, and John Condeelis. 2008. WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. Journal of Cell Biology 180(6): 1245–1260. Wang, P., M.R. Bowl, S. Bender, J. Peng, L. Farber, J. Chen, A. Ali, Z. Zhang, A.S. Alberts, R.V. Thakker, A. Shilatifard, B.O. Williams, and B.T. Teh. 2008. Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice. Molecular and Cellular Biology 28(9): 2930–2940. Dent, Erik W., Adam V. Kwiatkowski, Leslie M. Mebane, Ulrike Philippar, Melanie Barzik, Douglas A. Rubinson, Stephanie Gupton, J. Edward Van Veen, Craig Furman, Jiangyang Zhang, Arthur S. Alberts, Susumu Mori, and Frank B. Gertler. 2007. Filopodia are required for cortical neurite initiation. Nature Cell Biology 9(12): 1347–1359. Eisenmann, Kathryn M., Richard A. West, Dagmar Hildebrand, Susan M. Kitchen, Jun Peng, Robert Sigler, Jinyi Zhang, Katherine A. Siminovitch, and Arthur S. Alberts. 2007. T cell responses in mammalian Diaphanous-related formin mDia1 knock-out mice. Journal of Biological Chemistry 282(34): 25152–25158. Gupton, Stephanie L., Katherine Eisenmann, Arthur S. Alberts, and Clare M. Waterman-Storer. 2007. mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. Journal of Cell Science 120(19): 3475–3487. Peng, Jun, Susan M. Kitchen, Richard A. West, Robert Sigler, Kathryn M. Eisenmann, and Arthur S. Alberts. 2007. Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian Diaphanous-related formin mDia1. Cancer Research 67(16): 7565–7571. 8

VARI | 2008 Brian Cao, M.D. Laboratory of Antibody Technology Dr. Cao obtained his M.D. from Peking University Medical Center, People’s Republic of China, in 1986. On receiving a CDC fellowship award, he was a visiting scientist at the National Center for Infectious Diseases, Centers for Disease Control and Prevention in Atlanta (1991–1994). He next served as a postdoctoral fellow at Harvard (1994–1995) and at Yale (1995–1996). From 1996 to 1999, Dr. Cao was a Scientist Associate in charge of the Monoclonal Antibody Production Laboratory at the Advanced BioScience Laboratories–Basic Research Program at the National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Dr. Cao joined VARI as a Special Program Investigator in June 1999 and was promoted to Senior Scientific Investigator in July 2006. Staff Quliang Gu, Ph.D. Ping Zhao, M.S. Tessa Grabinski, B.S. Students Guipeng Ding Jenna Manby Rui Sun Ning Xu Aixia Zhang 9

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