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2002 Scientific Report

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

Publications Collins,

Publications Collins, Colin, Stanislav Volik, David Kowbel, David Ginzinger, Bauke Ylstra, Thomas Cloutier, Trevor Hawkins, Paul Predki, Christopher Martin, Meredith Wernick, Wen-Lin Kuo, Arthur Alberts, and Joe W. Gray. 2001. Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Research 11(6): 1034–1042. Palazzo, Alexander F., Hazel L. Joseph, Ying-Jiun Chen, Denis L. Dujardin, Arthur S. Alberts, K. Kevin Pfister, Richard B. Vallee, and Gregg G. Gundersen. 2001. Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Current Biology 11(19): 1536–1541. From left to right, back row: Waller, Alberts, Matheson front row: Vankirk, Peng, Odomosu, Newman 11

Antibody Technology Laboratory Brian Cao, M.D. Dr. Cao obtained his M.D. from Beijing Medical University, 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 (1991–1994). He next served as a Postdoctoral Fellow at Harvard (1994–1995) and 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. Laboratory Members Staff Huiying Zhang, Ph.D. Ping Zhao, M.S. Jessica Kalbfleisch, B.S. Students Jennifer Edgar, B.S. Josie Clowney Paul Veldhouse Research Projects T he antibody technology facility produces, purifies, and characterizes monoclonal and polyclonal antibodies. Our laboratory works with investigators on a variety of research projects, including the identification and characterization of novel proteins; affinity purification for structural analysis; development of clinical immunodiagnostic methods and kits; and engineering and humanizing monoclonal antibodies that have potential application for clinical diagnosis, prognosis, and immunotherapy in cancers and infectious diseases. Hepatocyte growth factor/scatter factor (HGF/SF)-Met, a ligand-receptor pair, plays important roles in tumorigenesis, angiogenesis, and metastasis. Tumors with an autocrine loop of HGF/SF-Met are highly malignant and have a poor prognosis. We have generated a panel of monoclonal antibodies (mAbs) to the ligand and found some of them with biologic neutralizing activity when they are used in combination. We have characterized their antitumor effect both in vitro and in vivo. A panel of mAbs raised against the Met receptor extracellular domain has been generated; two of these mAbs are under further characterization for clinical imaging/diagnostic application. Both anti-ligand and receptor mAbs have been patented. Angiogenesis contributes significantly to the progression of cancer and, as tumors grow, they begin to produce a wider array of angiogenesis molecules. In collaboration with Brian Haab’s microarray technology core facility and James Resau’s cellular/molecular imaging core facility at VARI, we are developing xenograft animal models for several human cancers, including glioblastoma and soft-tissue sarcoma, in order to understand the correlation between key growth factors (VEGF, HGF/SF, EGF, etc.) and their receptors, which stimulate tumor angiogenesis and metastasis. Moreover, we seek to evaluate the effect of mAbs on these growth factors or receptors, individually or in combination, for potential clinical immunotherapeutic application. In collaboration with the University of Michigan, we are currently using our antibodies to HGF/SF and Met for clinical nuclear imaging diagnostic applications. We are in the process of characterizing several radiolabeled mAbs that have high affinity to this ligand-receptor in animal models bearing human tumors. In addition, we are using several combined polyclonal and monoclonal antibodies to analyze quantitatively the expression levels of various growth factors and their receptors in human cancer tissues and the levels of their normal counterparts from clinical specimens. These experiments may identify potential diagnostic and prognostic indicators for these diseases. Anthrax is a zoonotic disease transmissible from animal to man that is caused by the Grampositive, spore-forming bacterium Bacillus 12

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