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CSHL Cancer Center - Signal Transduction

The Signal Transduction Program is exploring 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
Linda Van Aelst, Ph.D.           Mikala Egeblad, Ph.D.

Mikala
Mikala Egeblad - Associate Professor

Tumor cells’ interactions with the tumor microenvironment influence growth, response to therapy, and ability to metastasize. The Egeblad’s lab main focus is on myeloid-derived immune cells that enhance angiogenesis and metastasis and suppress the cytotoxic response against tumors. Using mouse models and real-time imaging, they study how different types of myeloid cells are recruited to tumors (breast; pancreatic) and how their behaviors influence cancer progression, including metastasis and response to therapy.
 
Douglas
Douglas Fearon - Professor

Studies the interaction between cancer and the immune system, with a focus on how the tumor microenvironment suppresses the immune system. Using a mouse model of pancreatic cancer, the Fearon lab has discovered a way to eliminate this suppression, which has led to a drug for human pancreatic cancer that will enter phase 1 clinical trials in 2015.
Robert
Robert Maki - Professor

Focuses on translating basic research discoveries into clinical applications, including new diagnostics and therapeutics. With joint appointments at CSHL and Northwell Health, he is dedicated to expanding cancer research at both institutions. His own research focuses on understanding the biology soft-tissue and bone sarcomas to better identify therapies for patients with these and other forms of cancer.
Darryl
Darryl Pappin - Research Professor

Develops new methods of identifying and analyzing proteins in complex biological samples. Key areas of interest include protein and peptide identification, quantitation, and modification using mass spectrometry (MS). Studies changes in the proteome and post-translational modifications in tumors.  
Raffaella
Raffaella Sordella - Associate Professor

Uses proteomic and genomic techniques to identify the molecular mechanisms contributing to “oncogene addiction”, a condition that results in certain cancers being sensitive to the inhibition of one particular gene or gene product. The primary focus is on signaling pathways involving EGFR in lung cancer, a receptor targeted by Tarceva, and on mechanisms that contribute to resistance to these agents.
 
Nicholas
Nicholas Tonks - Professor

Studies the activities of protein kinases and phosphatases (PTPs) and how they are disrupted in disease.  Recent work defined new roles for PTPs in regulating signaling events in breast cancer, identifying three PTPs as novel potential tumor suppressors. In addition, he is working on developing small-molecule drugs that target specific PTPs and modulate HER2 signaling, which could offer new therapeutic options for breast cancer.
Lloyd
Lloyd Trotman - Professor

Aims to define the events (process?) leading to tumor development, progression and metastasis using a system called RapidCaP. By genetically reprogramming normal cells in mouse prostate through genome editing, we follow their migration out of the tissue into the blood stream and then to metastatic sites. We use single cell genomics to understand how spontaneous gene alterations dictate the process, which is becoming an indispensable approach for studying disease evolution and the mechanisms that lead to therapy resistance.  
David
David Tuveson - Professor

Developed genetically engineered ductal pancreatic cancer mouse models to study the biology and therapy of pancreatic cancer, including the role of stromal components and strategies to target Kras. Recently developed an “organoid” system for culturing human pancreatic cancer cells, which will enable extensive analysis using genetic and pharmacological probes. He will be leading efforts to develop a pre-clinical research facility at CSHL.
Linda
Linda Van Aelst - Professor

Studies the role and mechanisms by which the Ras and Rho GTPases affect cell growth control, differentiation and morphogenesis. Specifically focusing on the effects that Ras and Rho family members have on tumorigenesis and neuronal development. Currently working with Kenneth Chang on a functional genomics approach to discover new targets for metastatic lung cancer.
Johannes
Johannes Yeh - Research Assistant Professor/Mgr, Antibody & Phage Display

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.
Hongwu
Hongwu Zheng - Assistant Professor

Aims to define the complex biology of malignant glioma pathogenesis, with the ultimate goal of improving therapeutic approaches. Currently working on teasing out the differences between malignant glioma cells and neural progenitors – with the idea of targeting differentiation control pathways as a novel avenue for malignant glioma treatment.

2016

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’
When antioxidants are pro-cancer? | November 15, 2016
Recent research on antioxidant levels in the cells of pancreatic cancer patients is homing in on a new, safer avenue for treatment. And it’s not what you’d think based on the reputation antioxidants have gained in popular culture.
Pancreas and colon tumors reprogram the liver, causing wasting and short-circuiting body’s immune response | November 8, 2016
Research reveals a mechanism that causes wasting in cancer and tests a way to reverse it
Expert Explains: What’s the connection between antioxidants and cancer? | October 14, 2016 
Researcher and practicing doctor David Tuveson explains how this fits into what scientists have learned about the connection between antioxidants and cancer.
Our most common infection-fighting white blood cells can be hijacked to support cancer spread | October 19, 2016
Neutrophils eject DNA nets to trap invaders but can be commandeered by cancer cells to help cancers spread; the process is experimentally overcome in mice
Novel drug therapy kills pancreatic cancer cells by reducing levels of antioxidants | July 28, 2016
Reducing levels of antioxidants in pancreatic cancer cells can help kill them, suggesting an entirely new treatment strategy for the notoriously lethal illness.
Discovery of new ovarian cancer signaling hub points to target for limiting metastasis | July 10, 2016
A previously undiscovered pathway reveals how ovarian cells can be transformed into cancer cells, offering new drug targets that might be able to stave of metastatic 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.

2015

Masthead Cove Yacht Club raises over $7000 for CSHL cancer research at annual race | November 25, 2015
Members of the Masthead Cove Yacht Club raised $7,124 from their annual Masthead Race, donating proceeds to support cancer research conducted by CSHL Professor Nicholas Tonks. 
Joni Gladowsky Breast Cancer Foundation donates $80,000 to Cold Spring Harbor Laboratory | 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, raising $80,000 for cancer research at CSHL.
An immune system marker for therapy-resistant prostate cancer | June 4, 2015
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. This is often the situation with prostate cancer, one of the deadliest and most highly prevalent cancers. While hormone...
Tumor surroundings are shown to affect progression of different cancer subtypes | May 27, 2015
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, a team of researchers led by Associate Professor Mikala Egeblad at Cold Spring Harbor Laboratory (CSHL) found that two different mouse models of breast cancer progressed...
Scientists show the mammary gland ‘remembers’ prior pregnancy, spurring milk production | May 7, 2015
Anecdotal reports of nursing mothers have long suggested that giving milk is a lot easier in second and subsequent pregnancies, compared with a first pregnancy.
New signaling pathway discovered in HER2-positive breast cancer, and two potentially powerful drug targets | April 20, 2015
One of the most promising ideas in cancer treatment is to apply a lesson learned in the fight against AIDS (Acquired Immune Deficiency Syndrome): simultaneously attacking a pathological process at different points of weakness can, in some cases, deal a knock-out blow. Just as the so-called AIDS “cocktail” directs multiple...
Study revises standard theory of how PTEN, a critical tumor suppressor, shuts off growth signals | April 9, 2015
The gene called PTEN is one of the most important of the body’s natural tumor suppressors. When the gene is mutated or missing, as it is often observed to be in a host of cancers, growth signals affecting cells can get stuck in the “on” position, enabling cells to proliferate out of control.
3D culture system for pancreatic cancer has potential to change therapeutic approaches | January 15, 2015
Pancreatic cancer is one of the most deadly forms of cancer, with only 6 percent of patients surviving five years after diagnosis. Today, Cold Spring Harbor Laboratory (CSHL) and The Lustgarten Foundation jointly announce the development of a new model system to grow both normal and cancerous pancreatic cells in the laboratory...
A novel biomarker for mutant p53 could help pathologists assessing tumors during surgery | January 5, 2015
Researchers at Cold Spring Harbor Laboratory (CSHL) today report the discovery of a novel cellular biomarker that could make it comparatively easy for cancer surgeons to determine if a patient has a potentially lethal mutation in a protein called p53, the most powerful of the body’s natural tumor suppressors and often called...

Krishnan, N. and Krishnan, K. and Connors, C. R. and Choy, M. S. and Page, R. and Peti, W. and Van Aelst, L. and Shea, S. D. and Tonks, N. K. (2015) PTP1B inhibition suggests a therapeutic strategy for Rett syndrome. J Clin Invest 125(8) pp. 3163-3177.

Palm, W. and Park, Y. and Wright, K. and Pavlova, N. N. and Tuveson, D. A. and Thompson, C. B. (2015) The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1. Cell 162(2) pp. 259-270.

Roe, Jae-Seok and Mercan, Fatih and Rivera, Keith and Pappin, Darryl J and Vakoc, Christopher R (2015) BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia. Molecular Cell 58(6) pp. 1028-1036.

Akerman, M. and Fregoso, O. I. and Das, S. and Ruse, C. and Jensen, M. A. and Pappin, D. J. and Zhang, M. Q. and Krainer, A. R. (2015) Differential connectivity of splicing activators and repressors to the human spliceosome. Genome Biol 16(1) pp. 119.

Saiyin, H. and Ardito-Abraham, C. M. and Wu, Y. and Wei, Y. and Fang, Y. and Han, X. and Li, J. and Zhou, P. and Yi, Q. and Maitra, A. and Liu, J. O. and Tuveson, D. A. and Lou, W. and Yu, L. (2015) Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma. J Pathol 236(2) pp. 142-154.

Trotman, L. C. and Nowak, D. G. and Cho, H. and Herzka, T. and Watrud, K. and DeMarco, D. V. and Wang, V. M. and Senturk, S. and Fellmann, C. and Ding, D. and Beinortas, T. and Kleinman, D. and Chen, M. and Sordella, R. and Wilkinson, J. E. and Castillo-Martin, M. and Cordon-Cardo, C. and Robinson, B. D. (2015) Myc drives Pten/trp53-deficient proliferation and metastasis due to Il6-secretion and Akt-suppression via Phlpp2. Cancer Discovery 5(6) pp. 636-651.

Fan, G. and Aleem, S. and Yang, M. and Miller, W. T. and Tonks, N. K. (2015) Protein Tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and BRK. Journal of Biological Chemistry 290(26) pp. 15934-15947.

Klingler, S. and Guo, B. and Yao, J. and Yan, H. and Zhang, L. and Vaseva, A. V. and Chen, S. and Canoll, P. and Horner, J. W. and Wang, Y. A. and Paik, J. H. and Ying, H. and Zheng, H. (2015) Development of resistance to EGFR targeted therapy in malignant glioma can occur through EGFR dependent and independent mechanisms. Cancer Research 75(10) pp. 2109-2119.

Park, Jae-Hyun and Rasch, Morten Grønbech and Qiu, Jing and Lund, Ida Katrine and Egeblad, Mikala (2015) Presence of Insulin-Like Growth Factor Binding Proteins Correlates With Tumor-Promoting Effects of Matrix Metalloproteinase 9 in Breast Cancer. Neoplasia 17(5) pp. 421-433.

Ramesh, M. and Krishnan, N. and Muthuswamy, S. K. and Tonks, N. K. (2015) A Novel Phosphatidic Acid-Protein Tyrosine Phosphatase D2 Axis is Essential for ERBB2 Signaling in Mammary Epithelial Cells. Journal of Biological Chemistry 290(15) pp. 9646-9659.

Naguib, Adam and Bencze, Gyula and Cho, Hyejin and Zheng, Wu and Tocilj, Ante and Elkayam, Elad and Faehnle, Christopher R and Jaber, Nadia and Pratt, Christopher P and Chen, Muhan and Zong, Wei-Xing and Marks, Michael S and Joshua-Tor, Leemor and Pappin, Darryl J and Trotman, Lloyd C (2015) PTEN Functions by Recruitment to Cytoplasmic Vesicles. Molecular Cell 58(2) pp. 255-268.

Dos Santos, L. I. and Galvao-Filho, B. and de Faria, P. C. and Junqueira, C. and Dutra, M. S. and Teixeira, S. M. and Rodrigues, M. M. and Ritter, G. and Bannard, O. and Fearon, D. T. and Antonelli, L. R. and Gazzinelli, R. T. (2015) Blockade of CTLA-4 promotes the development of effector CD8+ T lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing NY-ESO-1. Cancer Immunol Immunother 64(3) pp. 311-23.

Yu, J. R. and Tai, Y. and Jin, Y. and Hammell, M. C. and Wilkinson, J. E. and Roe, J. S. and Vakoc, C. R. and Van Aelst, L. (2015) TGF-beta/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes Dev 29(3) pp. 250-61.

Fan, G. and Wrzeszczynski, K. O. and Fu, C. and Su, G. and Pappin, D. J. and Lucito, R. and Tonks, N. K. (2015) A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines. Biochem J 465(3) pp. 433-42.

Perna, D. and Karreth, F. A. and Rust, A. G. and Perez-Mancera, P. A. and Rashid, M. and Iorio, F. and Alifrangis, C. and Arends, M. J. and Bosenberg, M. W. and Bollag, G. and Tuveson, D. A. and Adams, D. J. (2015) BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model. Proceedings of the National Academy of Sciences of the United States of America 112(6) pp. E536-E545.

Crompton, J. G. and Sukumar, M. and Roychoudhuri, R. and Clever, D. and Gros, A. and Eil, R. L. and Tran, E. and Hanada, K. and Yu, Z. and Palmer, D. C. and Kerkar, S. P. and Michalek, R. D. and Upham, T. and Leonardi, A. and Acquavella, N. and Wang, E. and Marincola, F. M. and Gattinoni, L. and Muranski, P. and Sundrud, M. S. and Klebanoff, C. A. and Rosenberg, S. A. and Fearon, D. T. and Restifo, N. P. (2015) Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res 75(2) pp. 296-305.

Gampe, K. and Stefani, J. and Hammer, K. and Brendel, P. and Potzsch, A. and Enikolopov, G. and Enjyoji, K. and Acker-Palmer, A. and Robson, S. C. and Zimmermann, H. (2015) NTPDase2 and Purinergic Signaling Control Progenitor Cell Proliferation in Neurogenic Niches of the Adult Mouse Brain. Stem Cells 33(1) pp. 253-64.

Boj, Sylvia F and Hwang, Chang-Il and Baker, Lindsey A and Chio, Iok In Christine and Engle, Dannielle D and Corbo, Vincenzo and Jager, Myrthe and Ponz-Sarvise, Mariano and Tiriac, Hervé and Spector, Mona S and Gracanin, Ana and Oni, Tobiloba and Yu, Kenneth H and van Boxtel, Ruben and Huch, Meritxell and Rivera, Keith D and Wilson, John P and Feigin, Michael E and Öhlund, Daniel and Handly-Santana, Abram and Ardito-Abraham, Christine M and Ludwig, Michael and Elyada, Ela and Alagesan, Brinda and Biffi, Giulia and Yordanov, Georgi N and Delcuze, Bethany and Creighton, Brianna and Wright, Kevin and Park, Youngkyu and Morsink, Folkert H M. and Molenaar, I.  Quintus and Borel Rinkes, Inne H and Cuppen, Edwin and Hao, Yuan and Jin, Ying and Nijman, Isaac J and Iacobuzio-Donahue, Christine and Leach, Steven D and Pappin, Darryl J and Hammell, Molly and Klimstra, David S and Basturk, Olca and Hruban, Ralph H and Offerhaus, George Johan and Vries, Robert G J. and Clevers, Hans and Tuveson, David A (2015) Organoid Models of Human and Mouse Ductal Pancreatic Cancer. Cell 160(1-2) pp. 324-338.

Schlomann, U. and Koller, G. and Conrad, C. and Ferdous, T. and Golfi, P. and Garcia, A. M. and Hofling, S. and Parsons, M. and Costa, P. and Soper, R. and Bossard, M. and Hagemann, T. and Roshani, R. and Sewald, N. and Ketchem, R. R. and Moss, M. L. and Rasmussen, F. H. and Miller, M. A. and Lauffenburger, D. A. and Tuveson, D. A. and Nimsky, C. and Bartsch, J. W. (2015) ADAM8 as a drug target in pancreatic cancer. Nature Communications 6pp. 6175.

Additional materials of the author at
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