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.
- CSHL President Bruce Stillman wins Heineken Prize (2020)
- 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)
June 8, 2021
Innovative research and educational activities never stopped during the COVID-19 pandemic.
Adenovirus: After 40 years, a call to arms
May 21, 2021
Virus research done 40 years ago at CSHL provided an early foundation for today’s adenovirus-based treatments and vaccines.
DNA replication: A game of precision
April 25, 2021
A highly choreographed complex of molecules is vital to starting and synchronizing DNA replication during cell division.
LIVE At the Lab: Adenovirus – A look back at early CSHL research
April 9, 2021
President and CEO Bruce Stillman and Dean of Academic Affairs Terri Grodzicker discuss their adenovirus research in the 1980s.
How human cells coordinate the start of DNA replication
March 23, 2021
Researchers discover how human cells regulate DNA replication, an important part of cell division, in time and space.
DNA Learning Center Nigeria opens to local students
October 16, 2020
A small university in Nigeria hosts Africa’s first DNA Learning Center and plans to serve hundreds of students with hands-on genetics instruction.
The “ORC” twists, pinches, and dances around DNA
September 16, 2020
The Origin Recognition Complex (ORC) is a key piece of cellular machinery, fundamental to life, yet so far mysterious.
Replicating a genome starts with a twist, a pinch, and a bit of a dance
September 16, 2020
Researchers have their first high resolution look at how “ORC,” a human protein complex essential to life, moves.
How two CSHL programs adapted during the COVID-19 pandemic
July 16, 2020
Mikala Egeblad and David Micklos presented their work at the “Life Science Across the Globe” seminar series.
CSHL President Bruce Stillman wins Heineken Prize
June 2, 2020
CSHL President and CEO Bruce Stillman wins the Heineken Prize for his work on eukaryotic DNA replication.