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2004 Scientific Report

Recent Publications

Recent Publications Zhuo, Xiaoliang, Jun Gu, Melissa J. Behr, Pam J. Swiatek, Huadong Cui, Qing-Yu Zhang, Yingiu Xie, Doris N. Collins, and Xinxin Ding. 2004. Targeted disruption of the olfactory mucosa-specific Cyp2g1 gene: impact on acetaminophen toxicity in the lateral nasal gland and tissue-selective effects on Cyp2a5 expression. Journal of Pharmacology and Experimental Therapeutics 308(2): 719–728. Peng, Jun, Bradley J. Wallar, Akiko Flanders, Pamela J. Swiatek, and Arthur S. Alberts. 2003. Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Current Biology 13(7): 534–545. Wu, Lin, Jun Gu, Yan Weng, Kerri Kluetzman, Pam Swiatek, Melissa Behr, Qing-Yu Zhang, Xiaoliang Zhou, Qiang Xie, and Xinxin Ding. 2003. Conditional knockout of the mouse NADPHcytochrome p450 reductase gene. Genesis 36(4): 177–181. From left to right: Zahatnansky, Koeman, Swiatek, Motornao (front), Sisson (back) 44

Laboratory of Cancer Genetics Bin T. Teh, M.D., Ph.D. Dr. Teh obtained his M.D. from the University of Queensland, Australia, in 1992, and his Ph.D. from the Karolinska Institute, Sweden, in 1997. Before joining the Van Andel Research Institute, he was an Associate Professor of medical genetics at the Karolinska Institute. Dr. Teh joined VARI as a Senior Scientific Investigator in January 2000. He became Deputy Director for Research Operations in the fall of 2003. Staff Miles Chao-Nan Qian, M.D., Ph.D. Jun Sugimura, M.D., Ph.D. Min-Han Tan, M.D., MRCP Peng-Fei Wang, M.D. Jindong Chen, Ph.D. Laboratory Members Sok Kean Khoo, Ph.D. David Petillo, Ph.D. Chun Zhang, Ph.D. Eric Kort, M.S. Jon Ditlev, B.S. Katherine Kahnoski, B.S. Jared Knol, B.S. Students Mark Batten, B.S. Timothy Yaw Bediako, B.S. Visiting Scientist Jens Alms Research Interests Cancer formation is a multistep process that results from genetic instability in the cells. At the molecular level it is characterized by multiple alterations in genes that play key regulatory roles in various cellular functions. Our laboratory is interested in identifying and studying these genetic alterations in both hereditary cancers and their sporadic counterparts, with a major focus on kidney tumors. In our studies of hereditary kidney tumors, we have reported the identification of two breakpoint genes, NORE1 and LSAMP, in a family with multiple cases of clear cell renal cell carcinoma. We have further demonstrated that both genes behave like tumor suppressors and have lower expression in sporadic renal cell carcinoma. As part of an international consortium, we have been involved in cloning the gene for hyperparathyroidism–jaw tumor syndrome, HRPT2, which is characterized by parathyroid tumors, jaw tumors, and kidney cysts and tumors; the kidney involvement includes adult Wilms tumors, mixed epithelial and stromal tumors, and papillary RCC. We have developed a monoclonal antibody for HRPT2 and are currently testing its utility for western blotting and immunohistochemical staining. Currently, our focus is on the functional roles of these novel genes. In terms of sporadic kidney tumors, we have continued to perform gene expression profiles using both the spot microarray and Affymetrix GeneChip systems. To date, a total of 350 cases have been completed. We have identified the molecular signatures for different subtypes of tumors (molecular diagnosis), for prognostication, and for the prediction of drug response. Currently, we are focusing on data mining and validation by immunohistochemical staining. In addition to carrying out these research projects, our laboratory has provided core sequencing and cytogenetic services to the Institute. To date over 40,000 sequences have been performed. We have also performed cytogenetics studies including FISH, conventional CGH, and SKY in collaboration with internal and external researchers. External Collaborators We have extensive collaborations with researchers and clinicians in the United States and overseas. Recent Publications Sugimura, J., X.J. Yang, M.S. Tretiakova, M. Takahashi, B. Funton, C.-N. Qian, T. Fujioka, N.J. Volgelzang, and B.T. Teh. In press. Gene expression profiling of mesoblastic nephroma and Wilms tumors—comparison and clinical implications. Urology. 45

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