Bruce William Stillman

Bruce William Stillman, AO, FRS (born 16 October, 1953, in Melbourne, Australia) is a biochemist and cancer researcher who has served as the Director of Cold Spring Harbor Laboratory (CSHL) since 1994 and President since 2003. He has simultaneously served as the Director of its NCI-designated Cancer Center since 1992. During his leadership, CSHL has been ranked as the #1 institution in molecular biology and genetics research by Thomson Reuters. Stillman’s research focuses on how chromosomes are duplicated in human cells and in yeast Saccharomyces cerevisiae; the mechanisms that ensure accurate inheritance of genetic material from one generation to the next; and how missteps in this process lead to cancer. For his accomplishments, Stillman has received numerous awards, including the Alfred P. Sloan Prize in 2004 and the 2010 Louisa Gross Horwitz Prize, both of which he shared with Thomas J. Kelly of Memorial Sloan-Kettering Cancer Center.

Life and career

A native of Australia, Bruce Stillman obtained a Bachelor of Science degree with honors at The University of Sydney and a Ph.D. from the John Curtin School of Medical Research at the Australian National University. He then moved to Cold Spring Harbor Laboratory as a Postdoctoral Fellow in 1979 and has been at the Laboratory ever since, being promoted to the scientific staff in 1981. In 1994, he succeeded Dr. James D. Watson as Director of Cold Spring Harbor Laboratory, and was appointed President in 2003.

Stillman began his career at Cold Spring Harbor Laboratory in the early 1980s with investigations into how DNA is copied, starting with studying DNA replication of human adenovirus as a model. He then began to study how the genome of simian virus 40 (SV40) is duplicated in cells. Eventually his research focused on how cellular chromosomes are duplicated and how the entire process is regulated in cells, studying the process primarily in the yeast S. cerevisiae and in human cells. This work provided key insights into how both virus and cellular oncoproteins manipulate cellular physiology to bring about oncogenic transformation.

One of his most significant achievements was the biochemical reconstitution with purified proteins of the complete replication of the SV40 DNA genome. This system utilized the virus-encoded T antigen that binds to the SV40 virus origin of DNA replication, the start site for DNA synthesis, coupled with and purified human proteins , many of them discovered by Stillman and his colleagues. These proteins include RPA, RFC, PCNA, and the discovery that multiple DNA polymerases participate in the process of copying DNA, often switching from one polymerase to the other.

Another major accomplishment was the discovery of the human Origin Recognition Complex (ORC), a key protein made up of six subunits that binds to cellular origins of DNA replication and coordinates the entire process of initiating a complete cycle of DNA replication throughout the entire cell genome. Soon after the discovery of ORC, Stillman’s group identified other initiation proteins that together form the pre-replication complex (pre-RC), which makes chromosomes competent for the subsequent initiation of DNA replication during the S phase of the cell cycle . His group’s recent studies have revealed the intricate details of how the initiation of DNA replication is regulated throughout the cell cycle and the mechanisms that prevent DNA replication from occurring more than once during each cell cycle.

Stillman has also studied how the proteins associated with the cellular DNA are inherited as cells divide. The proteins that combine with DNA to organize the genome into a chromatin structure include histones. He discovered proteins such as Chromatin Assembly Factor-1 (CAF-1) that cooperate with the DNA replication machinery to assemble new histones onto the DNA and determined the mechanism of how chromatin is inherited.

Honors and awards

• Commonwealth Postgraduate Award (1976-1978)
• Damon Runyon-Walter Winchell Cancer Fund Fellow (1979-1980)
• Rita Allen Foundation Scholar (1982-1987)
• Merit Award - National Institutes of Health (1986)
• The Royal Society (London), Elected Fellow (1993)
• Julian Wells Medal, Genome Conference, Australia (1994)
• Ida Beam Visiting Professor-University of Iowa (1996)
• Order of Australia, AO (1999)
• National Academy of Sciences, Elected Foreign Associate (2000)
• American Academy of Microbiology, Elected Fellow (2000)
• Doctor of Humane Letters (honoris causa), Hofstra University (2001)
• Doctor of Science (honoris causa), New York Institute of Technology (2001)
• European Molecular Biology Organization, Associate Member (2001)
• Doctor of Science (honoris causa), Stony Brook University (2002)
• Alfred P. Sloan Prize for Cancer Research, (2004)
• Doctor of Science, (honoris causa), Long Island University (2007)
• *Curtin Medal for Excellence in Medical Research, John Curtin School of Medical Research, Australian National University (2007)
• Doctor of Science (honoris causa), University of Sydney (2008)
• American Academy of Arts and Sciences, Elected Member (2008)
• Louisa Gross Horwitz Prize, Columbia University (2010)
  

Professional activities

Bruce Stillman is a member of the Medical Advisory Board of the Howard Hughes Medical Institute and advises a number of other research organizations including the M.I.T. David H. Koch Institute for Integrative Cancer Research at M.I.T., the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia and the Lewis-Sigler Institute at Princeton University. He is past co-chair of the Board of Scientific Councilors of the National Cancer Institute and past vice-chair of the National Cancer Policy Board of the National Institute of Medicine. He currently serves as a member of the Board on Life Sciences of the National Research Council and as a member of the National Cancer Institute Board of Scientific Advisors.

Further reading

• Faculty page at Cold Spring Harbor Laboratory
  
• Bruce Stillman: Understanding the Chromosome Cycle. Harbor Transcript. Winter 2010 30: 2