Bruce William Stillman
Encyclopedia
Bruce William Stillman, AO
, FRS (born October 16, 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
.
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 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.
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.
Order of Australia
The Order of Australia is an order of chivalry established on 14 February 1975 by Elizabeth II, Queen of Australia, "for the purpose of according recognition to Australian citizens and other persons for achievement or for meritorious service"...
, FRS (born October 16, 1953, in Melbourne, Australia) is a biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
researcher who has served as the Director of Cold Spring Harbor Laboratory
Cold Spring Harbor Laboratory
The Cold Spring Harbor Laboratory is a private, non-profit institution with research programs focusing on cancer, neurobiology, plant genetics, genomics and bioinformatics. The Laboratory has a broad educational mission, including the recently established Watson School of Biological Sciences. It...
(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
Thomson Reuters
Thomson Reuters Corporation is a provider of information for the world's businesses and professionals and is created by the Thomson Corporation's purchase of Reuters Group on 17 April 2008. Thomson Reuters is headquartered at 3 Times Square, New York City, USA...
. Stillman’s research focuses on how chromosomes are duplicated in human cells and in yeast Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
; 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
Louisa Gross Horwitz Prize
Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
, both of which he shared with Thomas J. Kelly
Thomas J. Kelly (oncologist)
Thomas J. Kelly is an American cancer researcher whose work focuses on the molecular mechanisms of DNA replication. Kelly is also Director of the Sloan-Kettering Institute, the basic research arm of the Memorial Sloan-Kettering Cancer Center in New York City. As director, Kelly oversees over one...
of Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Memorial Sloan–Kettering Cancer Center is a cancer treatment and research institution founded in 1884 as the New York Cancer Hospital...
.
Life and career
A native of Australia, Bruce Stillman obtained a Bachelor of Science degree with honors at The University of SydneyUniversity of Sydney
The University of Sydney is a public university located in Sydney, New South Wales. The main campus spreads across the suburbs of Camperdown and Darlington on the southwestern outskirts of the Sydney CBD. Founded in 1850, it is the oldest university in Australia and Oceania...
and a Ph.D. from the John Curtin School of Medical Research
John Curtin School of Medical Research
The John Curtin School of Medical Research is a major biomedical research centre in Australia, and part of the Australian National University, Canberra. The school was founded in 1948, as a result of the vision of Australian Nobel Laureate Sir Howard Florey and Prime Minister John Curtin.The Nobel...
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
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...
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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
is copied, starting with studying DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
of human adenovirus as a model. He then began to study how the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of simian virus 40
SV40
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans...
(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 purified human proteins , many of them discovered by Stillman and his colleagues. These proteins include RPA
Replication protein A
Replication protein A is a protein that binds single-stranded DNA in eukaryotic cells. During DNA replication, RPA prevents single-stranded DNA from winding back on itself or from forming secondary structures. This keeps DNA unwound for the polymerase to replicate it...
, RFC
Replication factor C
The replication factor C, or RFC, is a five-subunit protein complex that is required for DNA replication.The subunits of this heteropentamer are named Rfc1, Rfc2, Rfc3, Rfc4, and Rfc5 . RFC is used in eukaryotic replication as a clamp loader, similar to the γ Complex in E. coli. Its role as clamp...
, PCNA
PCNA
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome...
, 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
Origin Recognition Complex
ORC or Origin Recognition Complex is a multi-subunit DNA binding complex that binds in all eukaryotes in an ATP-dependent manner to origins of replication....
(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-replication complex
A pre-replication complex is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the...
(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
CHAF1A
Chromatin assembly factor 1 subunit A is a protein that in humans is encoded by the CHAF1A gene.-Interactions:CHAF1A has been shown to interact with ASF1B, ASF1A, MBD1, Bloom syndrome protein and CBX5.-Further reading:...
(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 SocietyRoyal SocietyThe Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
(London), Elected Fellow (1993) - Julian Wells Medal, Genome Conference, Australia (1994)
- Ida Beam Visiting Professor-University of IowaUniversity of IowaThe University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees...
(1996) - Order of AustraliaOrder of AustraliaThe Order of Australia is an order of chivalry established on 14 February 1975 by Elizabeth II, Queen of Australia, "for the purpose of according recognition to Australian citizens and other persons for achievement or for meritorious service"...
, AO (1999) - National Academy of SciencesUnited States National Academy of SciencesThe National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
, Elected Foreign Associate (2000) - American Academy of Microbiology, Elected Fellow (2000)
- Doctor of Humane Letters (honoris causa), Hofstra UniversityHofstra UniversityHofstra University is a private, nonsectarian institution of higher learning located in the Village of Hempstead, New York, United States, about east of New York City: less than an hour away by train or car...
(2001) - Doctor of Science (honoris causa), New York Institute of TechnologyNew York Institute of TechnologyNew York Institute of Technology is a private, non-sectarian, co-educational research university in New York City. NYIT has five schools and two colleges, all with a strong emphasis on technology and applied scientific research...
(2001) - European Molecular Biology OrganizationEuropean Molecular Biology OrganizationEMBO stands for excellence in the life sciences. The EMBO mission is to enable the best science by supporting talented researchers, stimulating scientific exchange and advancing policies for a world-class European research environment....
, 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 UniversityLong Island UniversityLong Island University is a private, coeducational, nonsectarian institution of higher education in the U.S. state of New York.-History:...
(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 SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
, Elected Member (2008) - Louisa Gross Horwitz PrizeLouisa Gross Horwitz PrizeLouisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
, Columbia UniversityColumbia UniversityColumbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
(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 ResearchWalter and Eliza Hall Institute of Medical Research
The Walter and Eliza Hall Institute of Medical Research is Australia's oldest medical research institute.In 2011, the institute is home to more than 650 researchers who are working to understand, prevent and treat diseases including blood, breast and ovarian cancers; inflammatory diseases such as...
in Melbourne, Australia and the Lewis-Sigler Institute at Princeton University
Princeton University
Princeton University is a private research university located in Princeton, New Jersey, United States. The school is one of the eight universities of the Ivy League, and is one of the nine Colonial Colleges founded before the American Revolution....
. He is past co-chair of the Board of Scientific Councilors of the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
and past vice-chair of the National Cancer Policy Board of the National Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
. He currently serves as a member of the Board on Life Sciences of the National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...
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