Research Highlights, 1890 - 2007
1890 - Biological Laboratory at Cold Spring Harbor founded.

1908 - George Schull finds that by cross-pollinating corn plants, he can consistently produce higher yielding progeny. This theory of “hybrid vigor” has become widely known and has found many applications in agriculture and genetics.

1928 - E. Carleton MacDowell discovers a strain of mice predisposed to spontaneous leukemia. Subsequent breeding experiments lead to the development of mice with increased susceptibility or resistance to the cancer. This work laid the foundation of modern cancer research.

1930 - The first treatment for Addison’s disease - adrenal cortical hormone - is purified at Cold Spring Harbor Laboratory.

1945 - Milislav Demerec greatly increased wartime penicillin production by isolating a high yielding strain of the filamentous fungus Penicillium chrysogenum.

1951 - At the CSH Symposium, Barbara McClintock describes "controlling elements" which she found can switch other genes on and off as a consequence of their movement within the genome. In 1983, McClintock was awarded the Nobel Prize for her discoveries concerning controlling elements, commonly known as "jumping genes."

1952 - Alfred Hershey and Martha Chase carry out the classic "Waring blender" experiment which reinforced the idea that the genetic material is DNA, not protein.

1953 - James Watson gives the first public description of the newly-discovered DNA structure at the CSH Symposium. The discovery influences virtually all subsequent biological and medical research.

1962 - James Watson, Francis Crick, and Maurice Wilkins share the Nobel Prize for the discovery of the double helix structure of DNA.

1969 - Alfred Hershey is awarded the Nobel Prize for work he conducted on his own, with Martha Chase, and in collaboration with Max Delbrück and Salvador Luria (who received the prize along with Hershey).

1972 - Phil Sharp, William Sugden, and Joe Sambrook develop a technique for separating and visualizing DNA fragments that today is used worldwide.

1973 - Rich Roberts begins to purify large numbers of restriction enzymes, the molecular "scissors” that cut DNA at specific sequences. His group discovers many of the restriction enzymes used in recombinant DNA technology.

1977 - Rich Roberts, Louise Chow, Thomas Broker, and Richard Gelinas discover “split genes” in adenovirus. Roberts and Phil Sharp share the Nobel Prize in 1993 for their roles in this discovery.

1980 - Ronald McKay and Birgit Zipser develop monoclonal antibodies to study the nervous system of the leech.

1981 - Mike Wigler and his collaborators clone the first human, tumor-derived oncogene, H-ras. Wigler later identifies a key oncogenic (cancer-causing) mutation in H-ras and discovers that the distantly related budding yeast also has RAS genes.

1982 - Jim Hicks, Amar Klar, and Jeff Strathern determine the molecular mechanism of mating-type switching in yeast. Their results have important implications for understanding the complexities and dynamics of chromosome structure and gene regulation in many complex organisms.

1983 - Barbara McClintock is awarded the Nobel Prize for her discovery of mobile genetic elements ("jumping genes").

1988 - An important functional link between the two general classes of cancer causing genes (oncogenes and tumor-suppressor genes) is established by Ed Harlow and his colleagues. They show that the product of a viral oncogene acts by binding to the product of a tumor suppressor gene.

Winship Herr characterizes the POU domain, a conserved protein motif which defines a large family of transcription factors.

Late 1980s - David Beach and others begin to uncover the universal molecular events that control the cell cycle (how and when cells divide) in organisms ranging from yeast to humans.

1990 - Carol Greider clones a gene that encodes a component of an enzyme–telomerase–that maintains the integrity of the tips of chromosomes (telomeres).

1990s - David Beach and his colleagues begin to study the cell cycle in human cells, which leads to the discovery of many genes associated with human cancers.

1992 - Carol Greider, Bruce Futcher, and their colleagues show an association between telomere shortening and cell aging. This discovery suggests a possible reason for the unchecked proliferation of cancer cells.

Bruce Stillman and his colleagues purify a protein complex (ORC) that is required to trigger DNA replication in complex organisms including humans.

Robert Martienssen and colleagues devise a "gene-trap" system for the plant Arabidopsis that employs transposable elements.

1993 - Richard Roberts is awarded the Nobel Prize for his 1977 co-discovery of “split genes.” Roberts shares the Prize with former CSHL colleague Phil Sharp (who made the same discovery independently at MIT).

Mike Wigler and Nikolai Lisitsyn develop Representational Difference Analysis (RDA), a powerful tool for identifying mutations in cells with complex genomes.

1994 - Bruce Stillman and his colleagues complete a 10-year effort to reconstitute DNA replication with purified human-cell proteins.

Tim Tully, Jerry Yin, and Alcino Silva make key discoveries about the molecular basis of learning and memory in Drosophila and mice.

1996 - Scott Lowe and colleagues at Stanford University discover why certain tumors are resistant to chemotherapy.

W. Richard McCombie and Rob Martienssen establish the first global collaboration to sequence the entire genome of a flowering plant (Arabidopsis).

Yi Zhong discovers a role for the ras oncogene in learning and memory.
Former and future CSHL scientists Amar Klar and Shiv Grewal show that in some instances, the stable inheritance of genetic traits depends not only on DNA, but rather on DNA plus associated proteins.

1997 - Mike Wigler, Nick Tonks and their colleagues use RDA to identify the P-TEN tumor suppressor gene. They find that this gene is mutated in a large percentage of sporadic breast, prostate, and brain tumors.

1998 - After discovering "condensins" in 1997, Tatsuyana Hirano and his colleagues discover "cohesins." These related proteins modulate chromosome structure in preparation for cell division.

Yi Zhong discovers why defects in the NF1 gene cause both cancer and learning defects. This work is an important advance in understanding one of the most frequently inherited disorders affecting humans, neurofibromatosis.

1999 - Roberto Malinow and Karel Svoboda provide some of the first real-time, high-resolution images of the events that alter the number and strength of connections between neurons within an important site for learning and memory in the brain, the hippocampus.

Scott Lowe discovers why many human tumors are deficient in p53 tumor suppressor function despite the presence of normal p53 genes. This work has important implications for the proper diagnosis and treatment of cancer.

Dmitri Chklovskii develops a mathematical "wiring economy" principle that explains how neurons are positioned and connected in the brain so as to minimize the length - and hence the volume - of wiring between neurons.

2000 - Adrian Krainer and Michael Zhang discover why particular mutations in the BRCA1 gene predispose individuals to breast and ovarian cancer (the mutations disrupt "splicing enhancers").

Roberto Malinow obtains evidence that supports the use of benzodiazepines in the treatment of familial Alzheimer's disease.

W. Richard McCombie, Rob Martienssen and the Arabidopsis Genome initiative report the first complete genome sequence of a plant species.

Leemor Joshua-Tor, Arne Stenlund and their colleagues determine the shape and biochemical properties of a protein required for papillomavirus DNA replication. Papillomavirus infection is associated with virtually every case of human cervical cancer.

2001 - W. Richard McCombie, Lincoln Stein and their colleagues contribute to a landmark achievement in biological and biomedical research: the analysis of a >90% complete draft of the human genome.

2002 - Masaaki Hamaguchi and Michael Wigler discover the DBC2 tumor suppressor, a gene that is inactive in 60% of the most common forms of breast cancer, and is also altered in the majority of lung cancers.

Roberto Malinow obtains evidence that the dynamic replacement of AMPA receptors at synapses is likely to be a principle molecular mechanism of memory. In related studies, Malinow and Linda Van Aelst reveal the role of Ras and Rap proteins in controlling AMPA receptor trafficking.

2003 - Tim Tully and Josh Dubnau identify a large group of candidate memory genes that are potential targets for the development of therapies for treating human memory disorders.
Yi Zhong finds that expressing human Aß42 protein in the Drosophila brain is sufficient to trigger the plaque formation, nerve cell death, and memory loss associated with Alzheimer’s disease in humans.

CSHL scientists and their colleagues from some 20 genome research centers around the world publish the finished sequence and their initial analysis of the 3 billion letter human genome.

2004 - David Spector develops the first system for viewing how the "Central Dogma" of biology unfolds in its entirety, from DNA to RNA to protein, within living cells.

Scott Lowe and colleagues establish a promising combination therapy for treating many cancers that do not respond to traditional chemotherapy.

Gregory Hannon creates the first library of human RNA interference (RNAi) clones, which enables a wide variety of users to rapidly identify and validate target genes involved in disease.

2005 - Greg Hannon, Scott Lowe, and Scott Powers discover that “microRNAs” can play an important role in tumor progression and metastasis.

Alea Mills and her colleagues discover that the loss of a gene called p63 accelerates aging in mice. Similar versions of the gene are present in many organisms, including humans. The p63 gene is thus likely to play a fundamental role in aging.

Bioinformatics researcher Lincoln Stein and his colleagues in the International HapMap Consortium publish the first comprehensive collection of genetic variations in the world’s human population. This first version of the HapMap is already accelerating the search for genes involved in common diseases including cancer, heart disease, diabetes, asthma, and macular degeneration.

By determining the molecular structure of a protein that enables malaria parasites to invade human red blood cells, structural biologist Leemor Joshua-Tor uncovers valuable clues for rational anti-malarial drug design and vaccine development.

David Spector and his colleagues discover a new molecular mechanism that is likely to control the production of many proteins in humans and other organisms. A deeper understanding of this rapid response, "cut and run" mechanism is predicted to have broad implications for biology and biomedical research.

Carlos Brody develops a strikingly simple yet robust mathematical model of how short-term memory circuits are likely to store, process, and make rapid decisions about the information the brain receives from the world.

Dmitri Chklovskii discovers strongly preferred patterns of connectivity or “scaffolds” within the wiring diagram of the rat brain. The patterns are likely to correspond to modules that play an important role in brain function not only in rats, but also in humans.
Partha Mitra reveals an intriguing “one step back, two steps forward” effect of sleep on vocal learning in the zebra finch.

2006 – Scott Lowe, Michael Wigler, Greg Hannon, Robert Lucito, and Scott Powers identify two genes on chromosome 11 that are likely to have a role in liver cancer – the fifth most frequent neoplasm worldwide.

Marja Timmermans and colleagues show that the opposing activity of two small RNAs can control major developmental events in plants, establishing a paradigm likely to have broad implications for the biomedical sciences.

Zachary Mainen and colleagues are the first to show that neurons in the brain can integrate spatial and reward information.

2007 – Jonathan Sebat and Michael Wigler find a genetic distinction between sporadic and heritable forms of autism.

Adrian Krainer shows that the RNA splicing factor SF2/ASF can act as a cancer-causing protein by changing the alternative splicing of other genes critical for growth-control of cells.

Alea Mills identifies the protein, CHD5, as a master gene of a tumor suppressive network.
Scott Lowe and colleagues show that continuous inactivation of the p53 tumor suppressor pathway is required to maintain tumors in later stages of cancer.


http://www.cshl.edu/History/research.html

quote -
Researchers, however, have not yet cured any disease or even routinely turned embryo cells into specific adult cells. They got furthest in mice, where they converted mouse stem cells into brain cells like those lost in Parkinson's and into blood cells.

Dr. Ronald McKay, a stem cell researcher at the National Institute of Neurological Disorders and Stroke, counseled patience.

''We are essentially getting cells to differentiate without the rest of the embryo,'' Dr. McKay said. ''That has to be controlled and it has to be controlled in the lab. It's tricky stuff and it will take quite a while to figure out.''

''The problem is that everyone is looking for magic,'' Dr. McKay said. ''Academics are too.''

But, he said, to get to the next stage, when animals can routinely be cured of some diseases, like diabetes or Parkinson's, ''is likely going to take a new wave of technology or experiments.''