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Biochemistry and Molecular Biology

The 6th Annual Lawrence Grossman Lectureship

October 17, 2016

 

The Department of Biochemistry and Molecular Biology celebrated 6th Annual Lawrence Grossman Lectureship given by Dr. Thomas Kelly and entitled “DNA Replication, Mutation and Cancer.

 

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Thomas Kelly is the Benno C. Schmidt Chair of Cancer Research and Member, Memorial Sloan Kettering Cancer Center in Manhattan. Kelly received his Ph.D. (Biophysics) from Johns Hopkins University (JHU) in 1968 and his M.D. from the JHU School of Medicine a year later. Following a period of postdoctoral research in the Laboratory of Viral Diseases at the National Institutes of Health, he returned to the JHU SOM in 1972 as an Assistant Professor in the Department of Microbiology. Kelly quickly rose through the ranks to Professor. In 1982, Kelly was named the Boury Professor and Director of the Department of Molecular Biology and Genetics; he also served as the founding director of the Johns Hopkins Institute of Basic Biomedical Sciences. In 2002, after a 40-year-long association with Johns Hopkins, Dr. Kelly was named Director of the Sloan Kettering Institute, the basic research arm of the Memorial Sloan Kettering Cancer Center in Manhattan.

Dr. Kelly’s long-term research interests have focused on DNA replication and its regulation in eukaryotic cells. Kelly pioneered the use of DNA viruses as model systems for investigating the molecular mechanisms of eukaryotic DNA replication. He and his colleagues developed the first two cell-free systems that could be used to study the biochemistry of DNA replication in human cells. These systems specifically and efficiently replicated the virion DNA from two animal DNA tumor viruses, adenovirus and simian virus 40. Kelly’s work in the adenovirus system led to the discovery of protein-primed DNA chain elongation and in the SV40 system identified the large T-antigen as the primary replication initiator and proved that it contained specific replication-origin-binding and orgin-DNA-unwinding activities. Kelly’s laboratory also made seminal discoveries about the molecular roles of primate/human transcription factors, DNA polymerases and single-stranded-DNA binding proteins in the SV40 replication pathway. In the 1990s, Kelly began studies of DNA replication in the genetically-tractable fission yeast, Schizosaccharomyces pombe. His laboratory characterized the nature of replication origins in the fission yeast genome and identified the roles of multiple kinases in the assembly and activation of the origin-recognition-complex and other pre-replicative complexes that act at yeast replication origins.

More recently, Kelly turned his attention to the important question of how DNA replication is strictly regulated in eukaryotic cells. His current investigations are aimed at improving our understanding of how the timing of events in eukaryotic chromosome replication is coupled to the cell cycle. Additionally, Kelly seeks to elucidate how cell cycle “checkpoints” work to suppress potentially genotoxic alterations, such as DNA damage or perturbations in DNA synthesis.

In recognition of Kelly’s groundbreaking investigations of eukaryotic DNA replication, he was named a Fellow of the American Academy of Arts and Sciences (1989), and elected Member of the National Academy of Sciences (1992), Member of the American Philosophical Society (1998), and Member of the National Academy of Medicine (2000). He also has received multiple prestigious prizes, including the 2004 Alfred P. Sloan, Jr. Prize of the General Motors Cancer Research Foundation and the 2010 Louisa Gross Horwitz Prize of Columbia University.

PHOTOS COURTESY OF  TARA BISER 

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