Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.
Bruce Stillman’s lab studies the process by which DNA is copied within cells before they divide in two. Working with yeast and human cells, Stillman and colleagues have identified many of the cellular proteins that function at the DNA replication fork during the S phase, the portion of the cell-division cycle when DNA synthesis occurs. Among these proteins are those that facilitate the assembly of chromatin, the protein–DNA complexes that form the chromosomes. Current research focuses on the mechanism that initiates the entire process of DNA replication in eukaryotic cells. At the heart of this mechanism is a protein that binds to “start” sites on the chromosomes, called the Origin Recognition Complex, ORC. The Stillman lab is part of an ongoing collaboration that determined the cryo-EM structure of ORC proteins in complex with a group of proteins, called a helicase, that unwind DNA during replication. These images offer molecular insights into how the helicase is loaded onto DNA. Stillman’s research also focuses on the process by which duplicated chromosomes are segregated during mitosis. They found ORC at centrosomes and centromeres, structures that orchestrate chromosome separation during mitosis. At centromeres, ORC subunits monitor the attachment of duplicated chromosomes to the mitotic spindle that pulls the chromosomes apart when they are correctly aligned. Stillman’s team has discovered that mutations in the Orc1 protein alter the ability of ORC to regulate both DNA replication and centrosome duplication. These mutations have been linked to Meier–Gorlin syndrome, a condition that results in people with extreme dwarfism and small brain size, but normal intelligence.
- Canada Gairdner International Award (with John Diffley, 2019)
- American Association for Cancer Research, Elected Fellow of the AACR Academy (2019)
- Doctor of Science, (honoris causa), Clarkson University (2018)
- Science and Technology Award, City of Suzhou, China (2018)
- National Academy of Inventors, Elected Fellow (2016)
- Herbert Tabor Research Award, American Society for Biochemistry and Molecular Biology (2014)
- Australian Academy of Science, Elected Corresponding Member (2012)
- Louisa Gross Horwitz Prize, Columbia University (with Thomas Kelly; 2010)
- American Academy of Arts and Sciences, Elected Member (2008)
- Doctor of Science (honoris causa), University of Sydney (2008)
- Doctor of Science, (honoris causa), Long Island University (2007)
- Society of Surgical Oncology – American Cancer Society Basic Science Award and Lecture (2006)
- Curtin Medal for Excellence in Medical Research, Australian National University (2006)
- American Association for the Advancement of Science, Elected Fellow (2005)
- Alfred P. Sloan Prize, General Motors Cancer Research Foundation, (with Thomas Kelly; 2004)
- Doctor of Science (honoris causa), Stony Brook University (2002)
- 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)
- American Academy of Microbiology, Elected Fellow (2000)
- National Academy of Sciences, Elected Foreign Associate (2000); Member as of 2013
- Order of Australia, AO (1999)
- Julian Wells Medal, Lorne Genome Conference, Australia (1994)
- The Royal Society (London), Elected Fellow (1993)
May 20, 2019
Current discoveries about DNA and human genome position CSHL scientists to make life-changing breakthroughs that will improve the human condition.
An essay from the President: Biology for the planet
May 16, 2019
CSHL plant scientists are looking for solutions to the biggest questions in agriculture as environments are reshaped by climate change.
President Bruce Stillman wins prestigious Gairdner Award
April 2, 2019
Dr. Bruce Stillman, President & CEO of CSHL, has been awarded the 2019 Canada Gairdner International Award for his work on eukaryotic DNA replication.
CSHL President elected as AACR Academy Fellow
March 25, 2019
CSHL President and CEO Dr. Bruce Stillman has been elected to the AACR Academy as part of the 2019 Fellows class.
Big bold dreamers
December 10, 2018
Dreamers drive discoveries. CSHL honors its many scientists making big impacts in their respective fields.
Elisabeth R. Woods Foundation donates to cancer research
July 17, 2018
The Elisabeth R. Woods Foundation donated $30,000 for lung cancer research at their donor gathering, hosted at CSHL.
The case for open and inclusive science
June 8, 2018
America must continue to a place where the most talented people in the world want to live, study and work.
Nation’s cancer centers endorse HPV vaccination
June 8, 2018
Dr. Stillman and Dr. Tuveson joined with the leaders of other institutions nationwide in endorsing a statement regarding the HPV vaccine
Nature’s masterpiece: the brain
May 11, 2018
A message from President and CEO Dr. Bruce Stillman from the Spring 2018 Harbor Transcript on the innovative research happening at CSHL
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
Hossain, M. and Stillman, B. (2016) Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription. Elife, 5
Sheu, Y. J. and Kinney, J. B. and Stillman, B. (2016) Concerted activities of Mcm4, Sld3 and Dbf4 in control of origin activation and DNA replication fork progression. Genome Res, 26(3) pp. 315-330.
Li, H. and Stillman, B. (2012) The origin recognition complex: a biochemical and structural view. In: The Eukaryotic Replisome: a Guide to Protein Structure and Function. MacNeill, Stuart (Ed.). Subcellular Biochemistry. Subcell Biochem, 62 pp. 37-58. Springer.
Mazurek, A. and Luo, W. and Krasnitz, A. and Hicks, J. and Powers, R. S. and Stillman, B. (2012) DDX5 regulates DNA replication and is required for cell proliferation in a subset of breast cancer cells. Cancer Discovery, 2(9) pp. 812-825.
Nakano, S. and Stillman, B. and Horvitz, H. R. (2011) Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans. Cell, 147(7) pp. 1525-1536.Additional materials of the author at
CSHL Institutional Repository