Signal Transduction Mechanisms in the Kidney

Tony Pawson

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The ASN invites Tony Pawson, PhD, to present a state-of-the-art lecture on “Signal Transduction Mechanisms in the Kidney” during the plenary session on Sunday, November 1, from 8:30 to 9:30 a.m.

A distinguished investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, Dr. Pawson also is a professor in the department of molecular genetics at the University of Toronto. He leads the Dynactome Project, which studies protein interactions within human cells and defines the deviations that characterize malignancy at the systems level.

Internationally recognized for his work in cellular organization and signal transduction, Dr. Pawson has increased our understanding of how cells respond to their environment. He identified the basic mechanisms through which cells react to growth signals and how they communicate with each other.

Dr. Pawson’s laboratory focuses on how cells convert an external signal into an intracellular response and on the molecular principles underlying cellular organization. He showed that cellular proteins are constructed in a modular fashion of functional domains, many of which mediate specific protein-to-protein interactions. He identified the Src homology 2 (SH2) domain as the prototypic interaction module. Dr. Pawson demonstrated that these unique structures bind to specific phosphotyrosine-containing protein motifs located on activated growth factor receptors to induce cascades of intracellular signaling that control cellular growth and differentiation. This concept established one of the basic paradigms of signal transduction.

Using a combination of structural, biochemical, proteomic, and genetic tools, Dr. Pawson and his colleagues are investigating how the cell is wired through protein interactions. This research shows that tyrosine kinases and SH2 domains work in tandem to transmit commands from hormones that regulate cellular reproduction and metabolism to their targets within the cell. Dr. Pawson originally detected the integrated functions of tyrosine kinases and SH2 domains in the context of oncogene products necessary for the cancer-like behavior of cells. These discoveries have contributed to development of drugs that block the action of tyrosine kinases, thus arresting the production of some types of cancer cells.

Since the discovery of SH2 domains, dozens of other modular protein domains have been found to control protein-to-protein interactions, many of which Dr. Pawson’s laboratory continues to investigate. Dr. Pawson and his colleagues are researching the pathways involved in reciprocal cell signaling and processes such as axon guidance in the nervous system and spatial organization of cells in complex tissues.

Dr. Pawson is a Fellow of the Royal Societies of London and Canada, a Foreign Member of the National Academy of Sciences, and serves on scientific advisory boards for several organizations. He has received many awards, including the AACR-Pezcoller International Award for Cancer Research in 1998, the Dr. H.P. Heineken Prize for Biochemistry and Biophysics in 1998, and the Kyoto Prize in Basic Sciences in 2008 for his work and discoveries in signal transduction.

Dr. Pawson conducted his graduate training at the Imperial Cancer Research Fund in London and received his PhD in molecular biology from King’s College, University of London, in 1976.