SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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T U M O R C E L L B I O L O G Y P R O G R A M T U M O R C E L L B I O L O G Y P R O G R A M PROGRAM LEADER Kermit L. Carraway, Ph.D. Professor of Cell Biology and Anatomy DESCRIPTION OF PROGRAM The Tumor Cell Biology Program currently comprises 28 faculty members in 11 different departments at the University of Miami School of Medicine. Faculty members are chosen based on the potential of their research to contribute to important aspects in the understanding of cancer cell biology. Faculty members must have peer-reviewed cancer related research funding in a field aligned with the scientific goals of the program or be newly recruited faculty investigators. GOALS OF PROGRAM The overall goal of the Tumor Cell Biology Program is to develop knowledge in the area of cell biology that can be applied to translational research on neoplastic disease. The focus of the individual studies varies widely, from gene therapy to the ultrastructural analyses of protein; however, all investigators are involved in cutting-edge research using the developing methods of molecular biology and cell structural analysis to ask questions important to tumor cell biology. The specific aims of the program are to: 1) Understand how genetic information is maintained, transferred, and translated into functional cell proteins, a fundamental issue throughout the history of cancer research. 2) Determine how tumor cells interact with other cells and their environment, particularly the molecular species and associations that favor or disfavor those interactions. This issue is critically important for understanding metastasis of tumors, the process that usually determines mortality of cancer patients. 3) Determine how signaling pathways and molecules transmit and integrate information, which determines cell fate, including cell structure and function. Included in such analyses are the mechanisms by which the molecular components of signaling and metabolic pathways are localized in cells to perform their particular roles. All of these questions and approaches are important to understanding how tumor cells behave and determining whether specific tumor cell behaviors can be exploited in combating cancer. Developing such translational applications is the ultimate goal of the Tumor Cell Biology Program. PARTICIPANTS Burnstein, Kerry L., Ph.D. Molecular and Cellular Pharmacology Carraway, Kermit L., Ph.D. Cell Biology and Anatomy Deutscher, Murray P., Ph.D. Biochemistry and Molecular Biology D’Urso, Gennaro, Ph.D. Molecular and Cellular Pharmacology Fletcher, Terace M., Ph.D. Biochemistry and Molecular Biology Franzmann, Elizabeth J., M.D. Otolaryngology Han, Zhiyong, Ph.D. Biology Harris, Thomas K., Ph.D. Biochemistry and Molecular Biology King, Mary Lou, Ph.D. Cell Biology and Anatomy UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 65
T U M O R C E L L B I O L O G Y P R O G R A M Lampidis, Theodore J., Ph.D. Cell Biology and Anatomy Li, Jie, M.D., Ph.D. Dermatology and Cutaneous Surgery Liu, Chia-Yang, Ph.D. Ophthalmology Lokeshwar, Balakrishna L., Ph.D. Urology Lokeshwar, Vinata B., Ph.D. Urology Malhotra, Arun, Ph.D. Biochemistry and Molecular Biology Mayeda, Akila, Ph.D. Biochemistry and Molecular Biology Moraes, Carlos T., Ph.D. Neurology Perez, Aymee, Ph.D. Cell Biology and Anatomy Salas, Pedro J. I., M.D., Ph.D. Cell Biology and Anatomy Shonukan, Oluwatoyin, M.D. Medicine Singal, Rakesh, M.D. Medicine Slingerland, Joyce M., M.D., Ph.D., F.P.R.C. (C) Medicine Verde, Fulvia, Ph.D. Molecular and Cellular Pharmacology Weed, Donald T., M.D., F.A.C.S. Otolaryngology Welsh, Catherine F., M.D. Medicine Werner, Rudolf K., Ph.D. Biochemistry and Molecular Biology Wyche, James, Ph.D. Biology Zimmers, Teresa A., Ph.D. Surgery HIGHLIGHTS/DISCOVERIES • MUC4 expression potentiates the phosphorylation/activation of the ErbB2 and ErbB3 tyrosine kinase receptors induced by neuregulin, providing a mechanism by which MUC4 may contribute to tumor progression through changes in cell signaling pathways (K. Carraway). • MUC4 in mammary gland is regulated at the post-transcriptional level by extracellular matrix (basement membrane) and by transforming growth factor-beta. Responses to both of these are known to change during breast cancer progression (K. Carraway). • MUC4 overexpression increases primary tumor growth in nude mice, acting as an antiapoptotic agent in the growing tumors and in cell culture (K. Carraway). • MUC4 regulates the localization of the receptor tyrosine kinase ErbB2 in polarized epithelial cells (K. Carraway). • Vitamin D inhibits the cell cycle by promoting nuclear exclusion of cyclin dependent kinase 2, opening new avenues for prostate cancer therapy. Regulation of cdk2 localization represents a new regulatory paradigm in G1 to S- phase progression (K. Burnstein). • Pol ε is required for initiation of DNA replication, suggesting that it provides multiple functions in promoting DNA replication, one of which is to facilitate assembly of the DNA replication initiation complex (G. D’Urso). • Discovery of a new endoribonuclease, RNase G (M. Deutscher). • Oligoribonuclease is an essential component of mRNA degradation (M. Deutscher). • Development of an efficient, cell-free translation system for mammalian cells (M. Deutscher). • Discovery of CD44v3-containing isoforms in head and neck squamous cell tumor tissues and cell lines (E. Franzmann). 66 UM/Sylvester Comprehensive Cancer Center Scientific Report 2004
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G L O S S A R Y IFN—interferon IL
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SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

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