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CSHL Cancer Center

The CSHL Cancer Center is a basic research facility committed to exploring the molecular basis of human cancer. With support from the National Cancer Institute (NCI), our researchers are using a focused, multi-disciplinary approach to break new ground in basic tumor biology and develop innovative, advanced technologies.

The three research programs provide focus in Gene Regulation & Cell Proliferation; Signal Transduction; and Cancer Genetics. In addition, nine Shared Resources provide essential access to technologies, services, and expertise that enhance productivity. With a strong collaborative environment and open communication, the CSHL Cancer Center is able to make breakthroughs in cancer biology that are translating into real progress in cancer diagnostics and treatment.

Cancer research at CSHL dates back to 1969, which marked the initiation of the DNA tumor virus research program. At this time, researchers realized that understanding the fundamental molecular and cellular biology of eukaryotic cells would provide powerful insight into the processes of oncogenic transformation.

With early success, the program expanded, and in 1971 the Laboratory was awarded a Program Project Grant from the NCI to fund research on DNA tumor viruses. In the early 1980's, cancer research at CSHL grew to include the study of cellular oncogenes, yeast genetics, and cell growth and cell cycle control. The program was highly productive, with two researchers independently winning the Nobel Prize in Physiology or Medicine for work that was done during this period. These studies form the foundation of current cancer research at CSHL, which since 1987 has been part of the NCI-designated CSHL Cancer Center.

Senior Leadership
Bruce W. Stillman, Ph.D.
Deputy Directors:
Research Shared Resources Administration
David Tuveson, M.D., Ph.D.
Nicholas Tonks, Ph.D.
Denise Roberts, Ph.D.

Program Leaders
Cancer Genetics Signal Transduction Gene Regulation & Cell Proliferation 
W. R. McCombie, Ph.D.
Michael Schatz, Ph.D.
Linda Van Aelst, Ph.D.
Mikala Egeblad, Ph.D.
David L. Spector, Ph.D.
Christopher Vakoc, M.D., Ph.D. 
Cancer Center External Advisory Board
Stephen Burakoff, M.D.
Director of the Mt. Sinai Cancer Institute
Mount Sinai School of Medicine
Lewis Cantley, Ph.D.
Director, Meyer Cancer Center
Weill Cornell Medical College and
New York-Presbyterian Hospital
Walter Eckhart, Ph.D.
Department of Molecular & Cell Biology
The Salk Institute for Biological Studies
Richard Hynes, Ph.D.
Department of Biology
Massachusetts Institute of Technology

Larry Norton, M.D.
Deputy Physician-in-Chief
Breast Cancer Programs
Medical Director
Evelyn H. Lauder Breast Center
Memorial Sloan Kettering Cancer Center
Kornelia Polyak, M.D., Ph.D.
Department of Medicine, Medical Oncology  
Harvard Medical School and
Dana-Farber Cancer Institute
Cindy Quense, M.P.A.
Assistant Director of Administration
The David H. Koch Institute for
Integrative Cancer Research
Martine Roussel, Ph.D.
Department of Genetics and Tumor Cell Biology
St. Jude Children's Research Hospital



Novel isoform of the tumor suppressor p53 associated with EMTs and metastasis
Camila dos Santos, as a postdoctoral researcher in the Hannon lab, identified the epigenetic changes that occur after pregnancy in the mouse mammary gland. The work offers insight into how pregnancy early in life may protect against breast cancer later.
An interactive tool for the analysis of single-cell copy-number variation
The Schatz lab, in collaboration with the Wigler and Atwal labs, has developed a new interactive, open-source analysis program called Gingko that can be used to reduce the uncertainty of single-cell analysis and visualize patterns in copy number mutations across populations of cells.
Research reveals how Brd4, known AML drug target, promotes leukemia maintenance
Brd4 is a validated drug target for AML with an inhibitor in clinical trials, yet its precise function has remained unclear. In this study, the Vakoc lab defined how the protein cooperates with hematopoietic transcription factors to create a chromatin signaling cascade that offers additional potential drug targets.
Discovery of cancer drug targets using high content CRISPR screening
The Vakoc lab collaborated with Justin Kinney to develop a new screening method using CRISPR-Cas9 technology. The method targets protein domains, rather than the traditional 5’ exon of the gene, to reveal cancer dependencies and identify new drug targets.
Tumor cells mimic blood vessels to help cancer spread
The Hannon lab developed a novel mouse model for breast cancer heterogeneity and used it to identify clones that were highly metastatic. The team found that these cells formed tube-like structures that mimic blood vessels, and identified two genes that drive vascular mimicry, which is likely promote growth of the primary tumor as well as metastasis. 
DOCK4 mediates TGF-β’s pro-metastatic effects in lung cancer
The Van Aelst lab, in collaboration with Molly Hammell and Chris Vakoc, has found that TGF-β promotes metastasis at least in part by inducing the intracellular signaling molecule DOCK4 in lung adenocarcinoma cells. In human patients, elevated DOCK4 levels correlates with poor prognosis, making this pathway an attractive target for future drug discovery.
New signaling pathway in HER2-positive breast cancer cells suggests potential drug targets
The Tonks lab, in collaboration with Senthil Muthuswamy, has identified a novel signaling pathway, including at protein tyrosine phosphatase, that is required for highly aggressive HER2-positive tumor cells to grow. His work suggests two new drug targets for the disease, which might have a dramatic effect on the disease when inhibited in combination.
RNA splicing defects spur growth in breast cancer
SRSF1, a splicing factor, is a known oncogene and is overexpressed in many cancers. The Krainer lab has identified hundreds of splicing events that are regulated by SRSF1 and pinpointed at least one of the critical targets that helps to drive breast cancer.
New insights into how tumor suppressor PTEN turns off cell growth
The Trotman lab, in collaboration with the Pappin and Joshua-Tor labs, has found that the tumor suppressor PTEN uses microtubules to travel around the cell. The work challenges previous models for how the protein moves and provides new understanding that may be useful for targeted drug development.


Novel isoform of the tumor suppressor p53 associated with EMTs and metastasis
The Sordella lab, in collaboration with the Krainer lab, identified a major new isoform of the tumor suppressor p53, called p53Ψ and showed that it induces expression of markers of the epithelial-mesenchymal transition and enhances the motility and invasive capacity of cells.
Development of Organoid Models of Pancreatic Cancer
In collaboration with Hans Celvers at the University of Utrecht as well as Darryl Pappin and Molly Hammell, the Tuveson lab established the first organoid models of both normal and cancerous ductal pancreatic cells.
Evaluation of Circulating Tumor Cells
James Hicks and Michael Wigler have developed methods to perform copy number analysis and whole genome amplification from circulating tumor cells (CTCs). Their latest data for melanoma and prostate cancer patients demonstrate the potential for this type of analysis to guide personalized therapies, and to monitor tumor evolution in response to therapy.
Role of PTP1B in Ras-induced Senescence
The Tonks lab, in collaboration with the Pappin and Hannon labs found that premature senescence in H-RAS(V12)-transformed primary cells is a consequence of oxidative inactivation of PTP1B and inhibition of miRNA-mediated gene silencing.
DOCK4 in lung adenocarcinoma metastasis
The Van Aelst lab has identified the atypical Rac1 activator DOCK4 as a novel, key component of the TGF-β/Smad pathway that promotes lung adenocarcinoma cell extravasation and metastasis.
P53 Mutations Change Phosphatidylinositol Acyl Chain Composition
The Trotman, Pappin and Tuveson labs collaborated to develop a high-throughput mass spectrometry method that identifies and quantifies twenty different cellular phosphatidylinositol lipid acyl chains. The method enabled them to discover that the anchoring tails of lipid second messengers form an additional layer of PIP signaling in cancer that is linked to p53.
Role of Dicer in Maintaining Genome Stability
The Martienssen lab found that Dicer, a canonical RNAi protein, facilitates the release of transcription machinery from DNA during replication, thereby preventing collisions and protecting the genome from damage.
Identification of functional protein domains using CRISPR/Cas-9
The Vakoc lab collaborated with Justin Kinney to develop a high-performance CRISPR strategy for cancer drug target discovery. The method involves targeting CRISPR-Cas9 mutations to functional protein domains rather than 5’ exons of candidate genes.
Improved strategy for analysis of large biomedical datasets
Justin Kinney and Gurinder Atwal collaborated to show how a fundamental mathematical quantity called “mutual information” can be used to detect and quantify relationships between variables in large, noisy datasets.


Complex interactions between a tumor and nearby normal cells are essential for tumorigenicty. 
The Egeblad and Powers labs identified multiple fibroblast-secreted factors that promote tumorigenicity using parallel pathways. 
Structural characterization of key step in DNA replication
In collaboration with scientists at Brookhaven National Laboratory, the Stillman lab established the architecture of an essential component of eukaryotic DNA replication.
High resolution structure of human Argonaute proteins bound to RNA
The Joshua-Tor and Hannon labs collaborated to solve the structure of two human Argonaute proteins in complex with physiologically relevant guide RNAs. 
Clusters of cooperating tumor-suppressor genes are found in large regions deleted in common cancers
Michael Wigler, in collaboration with Alexander Krasnitz, James Hicks and Scott Powers, used a new computational method called CORES to propose an alternative to the “two-hit” hypothesis to explain how cancers arise.
Identification of a PTP1B inhibitor as potential treatment for breast cancer
Nick Tonks’ lab identified a novel allosteric inhibitor of PTP1B, a small molecule natural product, which is now being investigated as a treatment for HER2-positive breast cancer patients. 
Novel mechanism for induction of cellular senescence 
Adrian Krainer’s lab identified a novel oncogene-induced senescence mechanism that implicates spliceosomal and ribosomal components in non-canonical roles as regulators of a pathway critical for maintenance of cellular homeostasis. 
Discovery of potential treatment for AML
The Vakoc lab identified a role for Rnf20 in the pathogenesis of MLL-fusion leukemia.  As other small-molecule drugs targeting other E3 ligase proteins exist, RNF20 could be a new druggable target for AML therapy. 
The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells
The Spector lab, along with Sven Diederichs lab at the University of Heidelberg, showed that the long noncoding RNA MALAT1 is not only a prognostic biomarker for metastasis but also plays an active role in disease progression.
Characterization of mechanism of the Chd5 Tumor Suppressor
The Mills lab found that the major tumor suppressor Chd5 binds to histone H3, offering insight into how this protein regulates a diverse set of cancers.


Tumor suppressor activity for protein tyrosine phosphatase
The Tonks lab collaborated with the Muthuswamy lab to reveal that PTPRO acts as a tumor suppressor and can act as a prognostic marker for HER2-positive breast cancers.
Potential antisense methods for cancer therapy
The Krainer lab has developed antisense oligonucleotides as a potential therapeutic for cancer, targeting the pyruvate kinase M (PK-M2) gene which is crucial for aerobic glycolysis and proliferation in tumor cells.
Potential targeted therapy for breast cancer 
The Stillman lab demonstrated that the protein DDX5 regulates DNA replication and may be a viable drug target for cancers with the DDX5 gene locus overexpressed or amplified.
Improved assembly method for single molecule sequencing data
Michael Schatz and colleagues devised a method to correct errors in single molecule sequences, by combining long PacBio reads with shorter read sequencing data for > 99.9 percent base-call accuracy. 
Functional analysis of the protein phosphatase activity of PTEN
The Tonks and Van Aelst labs collaborated on functional analysis of the protein phosphatase activity of the tumor suppressor PTEN, finding that autoregulation is a critical component of PTEN control.
Single cell sequencing demonstrates how tumors progress 
Michael Wigler, in collaboration with W. Richard McCombie, Alex Krasnitz and James Hicks, applied single cell sequencing to individual cells from a primary breast tumor, which revealed marked genetic heterogeneity within a single tumor, and shed new light on how a tumor evolves.
Contribution of the tumor environment to resistance to chemotherapy
The Egeblad lab demonstrated that the microenvironment contributes critically to drug response by regulating the permeability of blood vessels around the tumor, and affecting the local recruitment of inflammatory cells. 


Comprehensive genomic DNA analysis of mast cell leukemia uncovers clues that could improve therapy
Mona Spector, working with Ivan Iossifov, Scott Lowe and collaborators at Northwell Health, identified two novel mutations from a patient with mast cell leukemia, an extremely aggressive subtype of acute myeloid leukemia, offering new possibilities for diagnosis and treatment.
Novel regulatory role of hydrogen sulfide in cell response to protein misfolding
The Tonks and Pappin labs collaborated to discover how the inactivation and reactivation of PTP1B serves as a novel mechanism to regulate protein synthesis machinery.
Structure of RITS complex explains its role in heterochromatin assembly and gene silencing
The Joshua-Tor lab and colleagues determined how the three components of the RNA-Induced Initiation of Transcriptional gene Silencing (RITS) interact with each other, offering insight into the establishment of heterochromatin and gene silencing.
Study reveals details of alternative splicing circuitry that promote cancer’s Warburg effect
The Krainer lab, along with colleagues from Harvard Medical School, showed that the splicing factor SRSF3 is a key determinant in regulating which isoform of pyruvate kinase is expressed in cancer cells, providing mechanistic insights into the complex regulation the Warburg effect.
New role for RNAi during chromosomal replication 
The Martienssen lab found that transcription and replication machinery are coordinated during DNA replication, demonstrating that an RNAi mediated mechanism removes RNA pol II from replicating DNA to allow the replication fork to progress. 
Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation
The Spector lab demonstrated that genes “bookmarked” by an acetylated histone (H4K5Ac) during interphase, which accelerates transcriptional activation after mitosis through recruitment of the bromodomain protein BRD4.
Discovery of a new prostate tumor suppressor gene
The Trotman lab and colleagues showed that phosphatase PHLPP1 is a prostate tumor suppressor, and loss in combination with PTEN is associated with metastatic disease.
Discovery of potential treatment for AML 
The Vakoc lab, in collaboration with the Lowe lab, found that the protein Brd4 is essential for acute myeloid leukemia. The results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy for the disease. 

Deputy Director, Cancer Center Scientific Programs
David Tuveson, M.D., Ph.D.

Cancer researchers at CSHL are using cutting-edge technology in innovative and collaborative studies to explore the basic biology underlying the disease. Our research can be divided into three main focus areas:

Cancer Genetics Program
Gene Regulation & Cell Proliferation Program
Signal Transduction Program

Deputy Director, Cancer Center Shared Resources
Nick Tonks, Ph.D.

The CSHL Cancer Center has nine shared resources that facilitate cancer research with state-of-the-art technology and integral services. With the support of world-class staff, these core facilities ensure that Cancer Center researchers have all the necessary tools to make breakthrough discoveries.

Animal Facility Flow Cytometry
Animal & Tissue Imaging Functional Genomics & Genetics
Antibody & Phage Display Facility Mass Spectrometry
Bioinformatics Microscopy
DNA Sequencing  
NCIlogo Cold Spring Harbor Laboratory is an NCI-designated Cancer Center. As a basic research institution, CSHL does not treat patients. Information about individual cancers is available at the NCI CancerNet. Questions about CSHL's cancer research program should be directed to our Public Affairs Department.