Signal Transduction
The Signal Transduction Program explores the molecular signals within and between cells that drive cancer. These researchers are developing innovative new models for human tumors and advanced imaging technology with a goal of identifying potential “druggable” targets and mechanisms of drug resistance in cancer. Current research is focused on identifying and targeting the signaling mechanisms and tumor-host interactions that drive cancer.
Program Co-leaders
The Signal Transduction Program has two major overarching themes: 1) Identifying and targeting signaling in cancer; and 2) Characterizing and attacking tumor-host interactions driving cancer. In addition, the Signal Transduction Program is working to develop improved models of cancer. Program members include experts who bring an in-depth understanding of different families of signaling proteins, integrated with investigators who have expertise in cutting-edge technologies and systems. As such, the program generates basic discoveries that can drive the development of new cancer therapies.
Extensive collaborations among Signal Transduction Program members and other CSHL Cancer Center Programs have combined novel model systems of cancer, RNA interference, CRISPR, and state-of-the-art molecular/cellular and biochemical/proteomics approaches. Most Signal Transduction Program members also have clinical collaborators, predominately with investigators at Northwell Health. This highly collaborative and innovative environment has led to breakthroughs in our understanding of the signaling networks and immune interactions that drive cancer.
Turning off the immune system is hard. Turning it on against cancer is easier.
January 10, 2018
he immune system’s awesome power has captivated Professor Douglas Fearon throughout over 45 years of study, both as a medical doctor and as a scientist. Yet just 10 years ago, he “didn’t believe in cancer immunology,” he admits frankly. Today, cancer drugs based on the idea of harnessing the immune system’s power are helping to...
Three Strohm Sisters Family Foundation donates $5,000 for research on lung cancer recurrence
January 8, 2018
On December 18, 2017, Ed Strohm of the Three Strohm Sisters Family Foundation presented CSHL Associate Professor Mikala Egeblad with a check for $5,000 to support her ongoing lung cancer research. This is the first donation Cold Spring Harbor Laboratory has received from the Long Island-based foundation, which is dedicated to the eradication of cancer....
One experiment: Bacteria-trapping DNA webs are repurposed by cancer cells
October 19, 2017
Cancer is infamous for repurposing molecules and mechanisms our body routinely uses to sustain itself. This remarkable 3D image, made by CSHL’s expert electron microscopist Stephen Hearn, dramatically captures one such mechanism, spider web-like structures made of DNA and studded with toxic enzymes. Normally, these webs are cast out into extracellular space by white blood...
Halfway around the world, a reunion of friends opens door to a cancer discovery
August 31, 2017
fter interviewing for a position in a pancreatic cancer lab at Cold Spring Harbor Laboratory, 7,000 miles from his hometown in South Korea, Chang-il Hwang did what many of us would: he posted about it on Facebook. Little did he know that he was rekindling a friendship that would pave the way to a long-sought...
Long-sought mechanism of metastasis is discovered in pancreatic cancer
July 27, 2017
An epigenetic factor reprograms gene enhancers, enabling cancer cells to “remember” an earlier developmental state Cold Spring Harbor, NY — Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power...
Newly discovered mutations impair key cell pathways in pancreatic cancer
May 8, 2017
Cold Spring Harbor, NY — By closely studying a part of the human genome that has not yet been carefully scrutinized in studies of cancer, researchers at Cold Spring Harbor Laboratory (CSHL) have found important new clues to the development of pancreatic cancer. The researchers looked exclusively at small segments of DNA called promoters in...
Pershing Square Sohn cancer research prize awarded to CSHL’s Dr. Mikala Egeblad
May 8, 2017
New York City and Cold Spring Harbor, NY — Cold Spring Harbor Laboratory (CSHL) Associate Professor Mikala Egeblad, Ph.D., has been awarded the Pershing Square Sohn Prize for Young Investigators in Cancer Research. The announcement was made today by The Pershing Square Sohn Cancer Research Alliance. This is the fourth year the Alliance has awarded the...
Alexa DeAngelis didn’t see a place for herself in science, so she’s making one
April 28, 2017
For Alexa DeAngelis, who was recently awarded a Fulbright scholarship, combining a desire to help people with a passion for biochemistry means designing her own position in the budding specialty of precision medicine. ust a few weeks into her freshman year as a pre-med student at Georgetown, Alexa DeAngelis went through what she calls a...
New research explains why even targeted therapies eventually fail in lung cancer
March 29, 2017
Cold Spring Harbor, NY — Nearly 50 years into the “war” on cancer, doctors possess weapons that once would have seemed magical in their tumor-killing specificity. The drug Tarceva (erlotinib), for example, can virtually erase all traces of aggressive lung cancer tumors in a subset of patients who bear a particular disease-driving mutation in a...
Discovery of distinct cell subtypes around tumors helps explain why pancreatic cancer is so hard to treat
February 23, 2017
Cold Spring Harbor, NY — Researchers have moved an important step closer to understanding why pancreatic cancer is so hard to treat. With a median survival of only 6 months and a 5-year survival rate of about 8%, patients tend to be diagnosed when the disease has already spread to other parts of the body—this...
Researchers identify “Achilles’ heel” of PTEN that helps drive prostate cancer progression
February 13, 2017
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.
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
December 9, 2016
Truncated p53 proteins, presumed unimportant, now point to new drug targets for some of ‘the hardest cancers’ Cold Spring Harbor, NY — Discovered in the 1970s, tumor suppressors are among the most important proteins in the body. A master regulator of growth—“the guardian of the genome”—the p53 protein monitors cell growth for errors. We rely...
When antioxidants are pro-cancer
November 15, 2016
Base Pairs podcast Fighting cancer is so difficult in part because the healthy cells we want to support often end up casualties in the crossfire of toxic treatments. This episode of Base Pairs is about how we might overcome this obstacle even in some of the most difficult cases: patients with pancreatic cancer. Of all...
No (real) moustache required to join the “Movember” party
November 15, 2016
Prostate cancer is the most common non-skin cancer among American men, but most of the prostate cancer researchers at CSHL have zero risk of developing the disease. he majority of the prostate cancer researchers at CSHL are part of the population that will never get this disease: women. Growing a mo’ for “Movember”—a men’s health...
Pancreas and colon tumors reprogram the liver, causing wasting and short-circuiting body’s immune response
November 8, 2016
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.
Our most common infection-fighting white blood cells can be hijacked to support cancer spread
October 19, 2016
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.
What’s the connection between antioxidants and cancer?
October 14, 2016
Recent findings in pancreatic cancer research demonstrate that antioxidants aren’t exactly the reliable guardians that they’re often made out to be in health food ads. Researcher and practicing cancer doctor David Tuveson explains how this fits into what scientists have learned about the connection between antioxidants and cancer. dvertisements for products like pomegranate juice tell...
Novel drug therapy kills pancreatic cancer cells by reducing levels of antioxidants
July 28, 2016
A strategy based on mimicking the suppression of antioxidant-promoting NRF2 Cold Spring Harbor, NY — Reducing levels of antioxidants in pancreatic cancer cells can help kill them, newly published research reveals, suggesting an entirely new treatment strategy for the notoriously lethal illness, in which less than 5 percent of patients survive 5 years. Although it...
Discovery of new ovarian cancer signaling hub points to target for limiting metastasis
July 10, 2016
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.
How healthy cells might help cancer survive
February 4, 2016
Cancer researcher Mikala Egeblad aims to make cancer-fighting drugs more effective by preventing healthy cells from helping the enemy survive. he battlegrounds of the war on cancer—the landscape of healthy cells and molecules that make up the tumor’s “microenvironment”—sometimes fade to the background in cancer research. But CSHL Associate Professor Mikala Egeblad and her team...
Masthead Cove Yacht Club raises over $7000 for CSHL cancer research at annual race
November 25, 2015
Cold Spring Harbor, N.Y. — Members of the Masthead Cove Yacht Club (MCYC) raised $7,124 from their annual Masthead Race on August 16. The proceeds were donated to support cancer research conducted by CSHL Professor Nicholas Tonks. The event has raised over $50,000 since it was started in 2006 in memory of the MCYC’s former...
Joni Gladowsky Breast Cancer Foundation donates $80,000 to Cold Spring Harbor Laboratory
July 24, 2015
Cold Spring Harbor, NY — On Monday, July 20, 2015, the Joni Gladowsky Breast Cancer Foundation held its 11th annual Play for the Cure Golf Outing at The Cold Spring Harbor Country Club in Huntington, NY. Surrounded by family and friends, Alison Gladowsky-Deblinger, Jason Gladowsky and Elliot Gladowsky presented a check for $80,000 to Cold...
An immune system marker for therapy-resistant prostate cancer
June 4, 2015
Interleukin-6 signaling plays role in switching mouse prostate cancer to more aggressive, therapy-resistant form Cold Spring Harbor, NY — You are a patient who has just been treated for a serious illness but neither you nor your doctor knows how likely it is that you—in comparison with other patients—will actually be helped by the treatment....
Tumor surroundings are shown to affect progression of different cancer subtypes
May 27, 2015
Treatments may need to be tailored not just to specific cancer types but also to factors distinguishing the environments in which they develop Cold Spring Harbor, NY — Our environment can have a major impact on how we develop, and it turns out it’s no different for cancer cells. In work published today in Neoplasia,...
Scientists show the mammary gland ‘remembers’ prior pregnancy, spurring milk production
May 7, 2015
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.
New signaling pathway discovered in HER2-positive breast cancer, and two potentially powerful drug targets
April 20, 2015
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.
Study revises standard theory of how PTEN, a critical tumor suppressor, shuts off growth signals
April 9, 2015
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.
One experiment: Cellular highways carry anti-cancer cargoes
April 9, 2015
Super-resolution microscopy provides the surprising answer We’re swimming deep inside the cytoplasm, the watery interior of a cell, which, at the scale of this image, is living room-sized. The membrane—the oily wall that protects everything inside—is perhaps 20 feet away. The green “threads” crisscrossing around us are microtubules, gossamer-thin cargo roads that project inward from...
3D culture system for pancreatic cancer has potential to change therapeutic approaches
January 15, 2015
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.
A novel biomarker for mutant p53 could help pathologists assessing tumors during surgery
January 5, 2015
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.
Building publication list.
Semir Beyaz
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.
Mikala Egeblad
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.
Douglas Fearon
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.
Tobias Janowitz
Cancer is a systemic disease. Using both laboratory and clinical research, my group investigates the connections between metabolism, endocrinology, and immunology to discover how the body’s response to a tumor can be used to improve treatment for patients with cancer.
Robert Maki
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.
Darryl Pappin
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.
Raffaella Sordella
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.
Nicholas Tonks
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.
Lloyd Trotman
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.
David Tuveson
Pancreatic cancer is an extremely lethal malignancy. 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.
Linda Van Aelst
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.
Johannes Yeh
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.