The CSHL Cancer Center is a basic research facility committed to exploring the fundamental biology of human cancer. With support from the National Cancer Institute (NCI) since 1987, our researchers have used a focused, multi-disciplinary approach to break new ground in basic tumor biology and develop innovative, advanced technologies. Research covers a broad range of cancer types, including breast, prostate, leukemia, glioma, pancreatic, sarcoma, lung, and melanoma.
Three Scientific Programs provide focus in Gene Regulation & Cell Proliferation; Signal Transduction; and Cancer Genetics. In addition, nine Shared Resources offer 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.
Members of the CSHL Cancer Center apply a multi-pronged approach—from genomic biology to animal models to detailed biochemistry—to interrogate the molecular mechanisms that drive tumor growth and metastasis. Building on this basic research, scientists at the Lab are translating their findings into novel therapeutics for many of the most intractable cancers. Much of this research is made possible through numerous collaborations with clinical partners, including a strategic alliance with the nearby Northwell Health System that connects CSHL scientists with clinicians and more than 16,000 cancer patients each year.
Deputy Director, Shared Resources
Deputy Director, Administration
Denise Roberts, 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.
Professor, Department of Genetics and Tumor Cell Biology, St. Jude Children’s Research Hospital
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.
|New Method Offers Earlier Detection for Lethal Prostate Cancer
Prostate cancer is common and largely nonlethal. But for some 21,000 men—a small percentage of the total, but a nonetheless substantial number—the disease is fatal. For earlier and more accurate detection, the Krasnitz and Wigler labs have devised a new method to analyze tumor biopsies to identify the most lethal forms of prostate cancer.
|Crystal Structures Reveal Cancer Enzymes in Action
Tutases are a class of enzymes that regulate the microRNA let-7—a gene that is commonly downregulated in cancers. The Joshua-Tor lab used x-ray crystallography to capture images of the enzyme in action, offering insight into how these potential cancer targets function.
|Algorithm Finds Novel Recurrent Mutations in Cancer Patients
The Tuveson lab, in collaboration with Dr. Michael Schatz, (now at Johns Hopkins University) has developed an algorithm to identify novel mutations in patient tumor samples. The research team applied the method, called GECCO, to pancreatic cancer samples and discovered multiple mutations, many of which were associated with a significant risk of poor prognosis for patients.
|High-Resolution View of the Complex that Initiates DNA Replication
The Stillman and Joshua-Tor labs collaborated to obtain the structure of the active human Origin Recognition Complex (ORC), the proteins that control the initiation of DNA replication. Using both cyro-EM and x-ray crystallography, the labs obtained a high-resolution image of the ORC proteins bound to DNA, providing insights into the most fundamental process in cell proliferation.
|Novel Insights into the Regulation of PTEN in Prostate Cancer
New research from the Trotman lab has revealed that, in prostate cancer, a protein known as Importin-11 is the ‘Achilles’ heel’ that is required for the stability of the PTEN tumor suppressor. In fact, loss of Importin-11 predicted relapse and metastasis in patients who had had their prostate removed.
|Extra Chromosome Has Surprising Effect on Cell Growth and Tumorigenesis
Copy number variation is a hallmark of most cancers, and it often serves as a driver of cell proliferation. Surprisingly, new research from the Sheltzer lab suggests that an extra chromosome alone is not enough to initially spur tumor growth. Rather, prolonged changes in chromosome number lead to genetic instability that ultimately causes uncontrolled cell proliferation.
|Muscle-Wasting Disease Reveals Links Between Metabolism and Immune Evasion
Many cancer patients suffer from extreme weight loss in a condition known as cachexia. The Fearon lab has found that this calorie deprivation can have profound implications for tumor immunology, allowing tumor cells to become resistant to immunotherapy.
|The Role of RNAi in Quiescence
Cancer forms when quiescent cells begin dividing and proliferating. New research from the Martienssen lab demonstrates that the RNAi machinery—which is often mutated in cancers—plays a key role in this transition, holding cells in quiescence.
|Tumors Hijack the Immune System to Promote Metastasis
The Egeblad lab made the surprising discovery that tumors take advantage of an immune defense to enhance metastasis. Breast cancer cells can induce the immune system to release webs of DNA and enzymes, known as NETs. These webs directly stimulate the cancer cell’s ability to invade, promoting metastasis.
|Feedback Loop Controls the Decision to Proliferate
New research from the Stillman lab has revealed that key components of the DNA replication machinery participate in a feedback loop to control cell proliferation. The proteins—which are often mutated in cancer—provide a direct link between replication and proliferation.
|Research Identifies Signaling Pathway that Drives Metastasis in Ovarian Cancer
The Tonks lab has identified a role for the non-receptor tyrosine kinase, FER, in the invasion and movement of ovarian cancer cells—two traits that are required for metastasis. The work points to a potential drug target that could limit the most aggressive form of the disease.
|New Method Rapidly Assays Copy Number Variation
Copy number variation is well known as a driver of tumorigenesis and metastasis. The Levy lab has developed a protocol, called SMASH, that combines wet lab techniques with a new computational algorithm to quickly and efficiently analyze copy number variation in cancer cells.
Director, 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|
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.
The biological landscape is made up of millions of variables that interact in complex and often seemingly random ways. I am applying principles from physical and computational sciences to the study of biology to find patterns in these interactions, to obtain insight into population genetics, human evolution, and diseases including cancer.
Are you really what you eat? Our goal is to uncover the precise mechanisms that link nutrition to organismal health and disease states at the cellular and molecular level. A particular focus in our lab is to understand how dietary perturbations affect the immune system and contribute to the risk of diseases that are associated with immune dysfunction such as cancer.
Currently the Director of the Functional Genomics Shared Resource at CSHL. His studies focus on shRNA, microRNA, RNA interference, and siRNA. The lab has studied cancer proliferation gene discovery through functional genomics.
Among the changes that occur during pregnancy, those affecting the breasts have been found to subsequently modify breast cancer risk. My laboratory investigates how the signals present during pregnancy permanently alter the way gene expression is controlled and how these changes affect normal and malignant mammary development.
Cancer cells are surrounded by immune cells, blood vessels, chemical signals and a support matrix – collectively, the tumor microenvironment. Most microenvironments help tumors grow and metastasize, but some can restrict tumors. My lab studies how to target the bad microenvironments and support the good ones to combat cancer.
I’m studying how to harness the power of the immune system to fight cancer. Our underlying premise is that the microenvironment within a tumor suppresses the immune system. We have found a way to eliminate this suppression in the mouse model of pancreatic cancer, which has led to development of a drug for human pancreatic cancer that will enter phase 1 clinical trials in 2015.
Only a small portion of the RNAs encoded in any genome are used to make proteins. My lab investigates what these noncoding RNAs (ncRNAs) do within and outside of cells, where regulators of their expression are located in the genome, and how perturbations of ncRNAs and their regulators contribute to disease.
As organisms develop, genes turn on and off with a precise order and timing, much like the order and duration of notes in a song. My group uses model organisms to understand the molecules that control the tempo of development. We also study how changes in the timing of gene expression contribute to diseases like cancer.
To ensure that cells function normally, tens of thousands of genes must be turned on or off together. To do this, regulatory molecules - transcription factors and non-coding RNAs – simultaneously control hundreds of genes. My group studies how the resulting gene networks function and how they can be compromised in human disease.
Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.
From regulating gene expression to fighting off pathogens, biology uses DNA sequence information in many different ways. My research combines theory, computation, and experiment in an effort to better understand the quantitative relationships between DNA sequence and biological function. Much of my work is devoted to developing new methods in statistics and machine learning.
Our DNA carries the instructions to manufacture all the molecules needed by a cell. After each gene is copied from DNA into RNA, the RNA message is "spliced" - an editing process involving precise cutting and pasting. I am interested in how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy.
How does cancer arise? It evolves from innocuous beginnings, as healthy cells accumulate mutations and transform into lethal tumor cells. I am developing mathematical and statistical tools to discover key genetic elements involved in the evolution of cancer, and in particular, metastatic tumors.
Cells are amazingly complex, with the ability to sense, and remember timing, location and history. I am exploring how cells store this information, and how their surroundings influence their communication with other cells. I am also developing various imaging and molecular sequencing methods for tracking genes, molecules, and cells to understand how cancer cells arise and evolve.
We have recently come to appreciate that many unrelated diseases, such as autism, congenital heart disease and cancer, are derived from rare and unique mutations, many of which are not inherited but instead occur spontaneously. I am generating algorithms to analyze massive datasets comprising thousands of affected families to identify disease-causing mutations.
Applies non-invasive imaging methods and develops new imaging reagents to facilitate the use of genetically engineered mouse models of cancer in pre-clinical and basic cancer research. As Director of Animal Imaging, he provides collaborative research support to investigators at both CSHL and neighboring institutions and will an important role in the pre-clinical research facility at CSHL.
With joint appointments at CSHL and Northwell Health, I am working to expand clinical cancer research at our institutions to provide new treatments for patients as well as greater insight into the biology of this complex set of diseases. In my own research, I am collaborating on research in soft-tissue and bone sarcomas to better understand the cancer microenvironment and epigenetics, targeting molecular weaknesses to halt cancer growth.
Chromosomes are covered with chemical modifications that help control gene expression. I study this secondary genetic code - the epigenome - and how it is guided by small mobile RNAs in plants and fission yeast. Our discoveries impact plant breeding and human health, and we use this and other genomic information to improve aquatic plants as a source of bioenergy.
Over the last two decades, revolutionary improvements in DNA sequencing technology have made it faster, more accurate, and much cheaper. We are now able to sequence up to 10 trillion DNA letters in just one month. I harness these technological advancements to assemble genomes for a variety of organisms and probe the genetic basis of neurological disorders, including autism and schizophrenia, better understand cancer progression and understand the complex structures of the genomes of higher plants.
Cells employ stringent controls to ensure that genes are turned on and off at the correct time and place. Accurate gene expression relies on several levels of regulation, including how DNA and its associated molecules are packed together. I study the diseases arising from defects in these control systems, such as aging and cancer.
Our genome can encode hundreds of thousands of different proteins, the molecular machines that do the work that is the basis of life. I use proteomics, a combination of protein chemistry, mass spectrometry and informatics, to identify precisely which proteins are present in cells - cells from different tissues, developmental stages, and disease states.
Nearly all tumors exhibit a condition known as aneuploidy – their cells contain the wrong number of chromosomes. We’re working to understand how aneuploidy impacts cancer progression, in hopes of developing therapies that can specifically eliminate aneuploid cancers while leaving normal cells unharmed.
I am a computer scientist who is fascinated by the challenge of making sense of vast quantities of genetic data. My research group focuses in particular on questions involving human evolution and transcriptional regulation.
Two challenges in cancer biology guide my work: first, how do tumors become addicted to certain gene products, and second, how do tumors develop resistance to anti-cancer drugs. I focus on the epidermal growth factor receptor (EGFR), which is both addictive when mutated and a common source of drug resistance. We are also identifying new targets for the treatment of lung cancer.
The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell¹s nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.
Despite the development of preventive vaccines, human papillomaviruses (HPVs) still infect more than five million women each year, significantly increasing their risk of cervical cancer. I am working to identify how HPV multiplies so that we may develop drugs that can defeat the virus once it has infected an individual.
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.
Cells must constantly react to what is happening around them, adapting to changes in neighboring cells or the environment. I study the signals that cells use to exchange information with their surroundings. Our group is finding drugs that target these signals and thus can treat diabetes, obesity, cancer, and autism spectrum disorders.
We have recently developed the first genetic mouse model for therapy and analysis of metastatic prostate cancer. Now we can test if and how modern concepts of cancer evolution can outperform the 80-year-old standard of care - hormone deprivation therapy - and turn lethal prostate cancer into a curable disease.
Pancreatic cancer is an extremely lethal cancer. On average, patients who are diagnosed with pancreatic cancer succumb to the disease within 6 months. Research is the only way to defeat pancreatic cancer. My lab is making progress toward finding a cure by detecting the disease earlier and designing novel therapeutic approaches.
Cancer cells achieve their pathogenicity by changing which genes are on and off. To maintain these changes in gene expression, cancer cells rely on proteins that interact with DNA or modify chromatin. My group investigates how such factors sustain the aberrant capabilities of cancer cells, thereby identifying new therapeutic targets.
Normal cell function relies on coordinated communication between all the different parts of the cell. These communication signals control what a cell does, what shape it takes, and how it interacts with other cells. I study these signaling networks to understand how they guard against cancer and neurological disorders.
Dr. James D. Watson, co-discoverer of DNA’s double helix, is a Nobel laureate, past president of Cold Spring Harbor Laboratory, and generous philanthropist.
Devastating diseases like cancer and autism can be caused by spontaneous changes to our DNA—mutations first appearing in the child, or in our tissues as we age. We are developing methods to discover these changes in individuals, tumors, and even single cells, to promote early detection and treatments
Studies the creation of engineered biologics such as antibodies, proteins and peptides, for therapeutics and translational medicine. The lab employs protein engineering and chemical biology approaches to develop therapeutic biologics acting on cell signaling machineries in order to abrogate pathological cellular behavior. He is currently the Director of CSHL Cancer Center Antibody Shared Resource- a collaborative resource for high quality antibody development.
My research group focuses on normal and malignant hematopoietic stem and progenitor cells, specifically early erythroid progenitors and leukemic stem cells. We are currently using both CRISPR/Cas functional genomic and forward chemical biology genetic approaches to uncover critical genes and small chemical compounds regulating the self-renewal of hematopoietic stem and progenitor cells. The ultimate goal of this work is to identify novel therapeutics for drug resistant cancer-related anemias and leukemias through targeting of novel self-renewal pathways and metabolic vulnerabilities.
I study a type of brain cancer known as malignant glioma, which differs from healthy tissue by a small number of defining characteristics. By forcing glioma cells to adopt these healthy traits, we can stop tumor growth. My group searches for therapeutic ways to force this transition.