Lurie Cancer Center Member
Robert A Lamb, PhD, ScD
Chairperson, Molecular Biosciences; Judd A. and Marjorie Weinberg College of Arts and Sciences
Signal Transduction in Cancer
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Dr. Lamb is an Investigator of the Howard Hughes Medical Institute and member of the National Academy of Sciences. Overall, his laboratory is interested in defining the mechanism of viral entry into target cells. Although, the viruses his laboratory focuses have no role in viral induced cancers, his work provides an important basis for work in the Viral Oncogenesis Program which is focused on the entry of viruses associated with human cancer. Influenza virus and the paramyxoviruses PIV5 (formerly known as SV5) and hPIV3 were selected for study by Dr. Lamb not only because of their importance as the causative agents of major diseases but also because they provide excellent models for examining a variety of properties of integral membrane proteins. As these proteins are the major antigenic determinants of the viruses, knowledge about their structure will enhance the understanding of how to develop new vaccines. In addition, some of the biochemical activities of the viruses are specialized to the virus, making them attractive as points of intervention in the virus life cycle to which rationally designed therapeutic agents can be developed. Several different projects are under study: (1) The mechanism by which viruses enter cells by virus-mediated membrane fusion and determination of the atomic structure of the viral fusion (F) protein; (2) The protein-protein interactions necessary for virus assembly; (3) The structure and function of the minimalistic influenza virus-encoded ion channels, M2, and BM2; (4) Endocytosis and degradations signals in viral glycoproteins, (5) The interaction of the multifunctional V protein of paramyxoviruses with cellular proteins to control the cell cycle and the interferon response to SV5 infection; (6) Using reverse genetics to understand viral pathogenesis. In 2005/6 in collaboration with Dr. Theodore Jardetzky, Dr. Lamb obtained the atomic structure of the paramyxovirus F protein both in its metastable pre-fusion conformation and in its post-fusion conformation . These two structures reveal the largest protein rearrangement observed in biology to date and provide a fascinating insight into the mechanism of virus-mediated membrane fusion. Further, several technical developments in protein expression that were made in our structural studies may be directly applicable to studies on other viral glycoproteins including those of EBV and all retroviruses.