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Nicholas Tonks

Nicholas Tonks

Professor
Caryl Boies Professor of Cancer Research

Ph.D., University of Dundee, 1985

tonks@cshl.edu | (516) 367-8846 (p)

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.

Nicholas Tonks and colleagues study a family of enzymes called protein tyrosine phosphatases, or PTPs, which remove phosphate groups from proteins and other signaling molecules, such as lipids, in cells. Disruption of PTP function is a cause of major human diseases, and several of the PTPs are potential therapeutic targets for such diseases. Tonks’ group seeks to fully characterize the PTP family, understanding how PTP activity is controlled and how PTPs modify signaling pathways. In addition, they are working to determine how those pathways are abrogated in serious illnesses, including cancer, diabetes, and Parkinson’s disease. The overall goal is to identify new targets and strategies for therapeutic intervention in human disease. Tonks and colleagues have defined new roles for PTPs in regulating signaling events in breast cancer, identifying three PTPs as novel potential tumor suppressors. They have characterized the regulation of PTP1B by reversible oxidation, demonstrating that it is regulated by covalent modification of the active site by hydrogen sulfide (H2S) under conditions of ER stress that are linked to protein-folding-related pathologies, such as Parkinson’s and Alzheimer’s. In addition, they have generated recombinant antibodies that selectively recognize the oxidized conformation of PTP1B; these antibodies display the ability to promote insulin signaling in cells and suggest novel approaches to therapy for diabetes. Finally, they have also discovered a novel mechanism for allosteric regulation of PTP1B activity, offering the possibility of developing small-molecule drugs that could inhibit the phosphatase and thereby modulate signaling by insulin and the oncoprotein tyrosine kinase HER2, potentially offering new ways to treat insulin resistance in type-2 diabetes and breast cancer.

Vallee Visiting Professor Award

    Nicholas Tonks wins prestigious ASBMB award

    Nicholas Tonks wins prestigious ASBMB award

    July 3, 2018

    CSHL Professor Nicholas Tonks, the Caryl Boies Professor of Cancer Research, has been awarded the American Society for Biochemistry and Molecular Biology (ASBMB)’s 2019 Earl and Thressa Stadtman Distinguished Scientist Award. Tonks’ research has largely focused on the protein tyrosine phosphatase (PTP) family of enzymes, the “inaugural member” of which, PTP1B, he discovered in late...


    Progress toward improved Wilson’s disease drug

    Progress toward improved Wilson’s disease drug

    June 27, 2018

    Cold Spring Harbor, NY — Researchers at Cold Spring Harbor Laboratory (CSHL), working in collaboration with DepYmed Inc., a CSHL spinout company, today report that they have conducted promising preclinical experiments on a compound that could be used to treat Wilson’s disease and possibly other disorders—including certain types of cancer—in which levels of copper in...


    Portrait of a Neuroscience Powerhouse

    Portrait of a Neuroscience Powerhouse

    April 27, 2018

    At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...


    Discovery of new ovarian cancer signaling hub points to target for limiting metastasis

    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.


    Masthead Cove Yacht Club raises over $7000 for CSHL cancer research at annual race

    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...


    Breaking down breast cancer at CSHL

    Breaking down breast cancer at CSHL

    October 30, 2015

    LabDish blog Breast cancer awareness is important, but it’s action that saves lives. Whether developing more accurate and affordable tests for patients or mapping out the treacherous landscape of breast cancer genetics, researchers at CSHL certainly aren’t putting the fight on pause even as the pink ribbons dissipate. Explore how they’re attacking breast cancer from...


    In mice, an experimental drug treatment for Rett syndrome suggests the disorder is reversible

    In mice, an experimental drug treatment for Rett syndrome suggests the disorder is reversible

    July 27, 2015

    Cold Spring Harbor, NY — A team at Cold Spring Harbor Laboratory (CSHL) has developed a strikingly new approach for treating Rett syndrome, a devastating autism spectrum disorder (ASD) that affects 1 in 10,000 people in the US, mostly girls. In a paper appearing online today in the Journal of Clinical Investigation, Professor Nicholas Tonks,...


    Joni Gladowsky Breast Cancer Foundation donates $80,000 to Cold Spring Harbor Laboratory

    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...


    New signaling pathway discovered in HER2-positive breast cancer, and two potentially powerful drug targets

    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.


    Cold Spring Harbor Laboratory and GSK to develop diabetes and obesity therapeutic

    Cold Spring Harbor Laboratory and GSK to develop diabetes and obesity therapeutic

    March 23, 2015

    Cold Spring Harbor, NY — Cold Spring Harbor Laboratory (CSHL) today announced a collaboration with GSK to develop a treatment for obesity and type 2 diabetes. Scientists at CSHL and GSK will pursue drug development based on a novel approach to regulate the enzymatic activity of the phosphatase PTP1B. The goal of the multi-year CSHL-GSK...


Krishnan, N. and Koveal, D. and Miller, D. H. and Xue, B. and Akshinthala, S. D. and Kragelj, J. and Jensen, M. R. and Gauss, C. M. and Page, R. and Blackledge, M. and Muthuswamy, S. K. and Peti, W. and Tonks, N. K. (2014) Targeting the disordered C terminus of PTP1B with an allosteric inhibitor. Nature Chemical Biology, 10(7) pp. 558-566.

Tonks, N. K. (2013) Protein tyrosine phosphatases - from housekeeping enzymes to master regulators of signal transduction. Febs Journal, 280(2) pp. 346-378.

Haque, Aftabul and Andersen, J. N. and Salmeen, A. and Barford, D. and Tonks, N. K. (2011) Conformation-Sensing Antibodies Stabilize the Oxidized Form of PTP1B and Inhibit Its Phosphatase Activity. Cell, 147(1) pp. 185-198.

Lin, G. and Aranda, V. and Muthuswamy, S. K. and Tonks, N. K. (2011) Identification of PTPN23 as a novel regulator of cell invasion in mammary epithelial cells from a loss-of-function screen of the 'PTP-ome'. Genes and Development, 25(13) pp. 1412-1425.

Krishnan, N. and Fu, C. and Pappin, D. J. and Tonks, N. K. (2011) H2S-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Science Signaling, 4(203)

Additional materials of the author at
CSHL Institutional Repository