Nicholas Tonks
Professor
Caryl Boies Professor of Cancer Research
Ph.D., University of Dundee, 1985
tonks@cshl.edu | (516) 367-8846
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
July 3, 2018
Professor Nicholas Tonks wins Earl and Thressa Stadtman Distinguished Scientist Award from the American Society for Biochemistry and Molecular Biology
Progress toward improved Wilson’s disease drug
June 27, 2018
Encouraging early results in a potential new treatment for Wilson's disease
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
The Joni Gladowsky Breast Cancer Foundation raises funds for breast cancer research
July 17, 2017
On July 10 2017, the Joni Gladowsky Breast Cancer Foundation held its annual golf tournament at Cold Spring Country Club.
Discovery of new ovarian cancer signaling hub points to target for limiting metastasis
July 10, 2016
A team of researchers at Cold Spring Harbor Laboratory discovers new insights into signaling events that underlie metastasis in ovarian cancer cells.
Masthead Cove Yacht Club raises over $7000 for CSHL cancer research at annual race
November 25, 2015
Members of the Masthead Cove Yacht Club (MCYC) raised $7,124 from their annual Masthead Race.
Breaking down breast cancer at CSHL
October 30, 2015
A look at how several researchers at CSHL contribute to the field of breast cancer research.
In mice, an experimental drug treatment for Rett syndrome suggests the disorder is reversible
July 27, 2015
A team at Cold Spring Harbor Laboratory find a new approach for treating Rett syndrome, a devastating autism spectrum disorder
Joni Gladowsky Breast Cancer Foundation donates $80,000 to Cold Spring Harbor Laboratory
July 24, 2015
These proceeds will support breast cancer research in the laboratory of CSHL Professor Nicholas Tonks.
New signaling pathway discovered in HER2-positive breast cancer, and two potentially powerful drug targets
April 20, 2015
Rsearchers discovered a new pathway, which contains at least two potentially powerful drug targets
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 atCSHL Institutional Repository