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.
Copper, cancer, and COVID-19: The story of an idea, a meeting, and a paper
March 4, 2022
The Copper Cancer Consortium started as a new treatment concept and is now a published paper. Read the story of Banbury's last meeting before COVID.
June 8, 2021
Innovative research and educational activities never stopped during the COVID-19 pandemic.
Nicholas Tonks named 2019 AAAS Fellow
November 26, 2019
CSHL Professor Nicholas Tonks is being honored as a 2019 AAAS Fellow for his work on signal transduction and the discovery of PTP.
Historic building—groundbreaking science
October 29, 2019
The Demerec building has been monumental in scientific history. Now, a $75 million renovation of this celebrated labspace will define CSHL’s future.
Possible treatment for Wilson’s disease unexpectedly identified
July 31, 2018
Dr. Nicholas Tonks describes how the serendipity inherent to basic research played its part in discovering a potential treatment for Wilson's disease.
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.
Drugging an undruggable target with Dr. Nicholas Tonks
July 12, 2016
A scientific journey from discovery research to a clinical trial.
18 Nov 2021 | Cancer Discovery
Wiede, Florian, Lu, Kun-Hui, Du, Xin, Zeissig, Mara, Xu, Rachel, Goh, Pei, Xirouchaki, Chrysovalantou, Hogarth, Samuel, Greatorex, Spencer, Sek, Kevin, Daly, Roger, Beavis, Paul, Darcy, Phillip, Tonks, Nicholas, Tiganis, Tony
11 Nov 2021 | Nature Reviews Cancer
Ge, Eva, Bush, Ashley, Casini, Angela, Cobine, Paul, Cross, Justin, DeNicola, Gina, Dou, Q, Franz, Katherine, Gohil, Vishal, Gupta, Sanjeev, Kaler, Stephen, Lutsenko, Svetlana, Mittal, Vivek, Petris, Michael, Polishchuk, Roman, Ralle, Martina, Schilsky, Michael, Tonks, Nicholas, Vahdat, Linda, Van Aelst, Linda, Xi, Dan, Yuan, Peng, Brady, Donita, Chang, Christopher
Author Correction: Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth.
29 Jan 2021 | Scientific Reports | 11(1):3036
Bencze, Gyula, Bencze, Szilvia, Rivera, Keith, Watson, James, Hidvegi, Mate, Orfi, Laszlo, Tonks, Nicholas, Pappin, Darryl
Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth
25 Aug 2020 | Scientific Reports | 10(1):14174
Bencze, G, Bencze, S, Rivera, K, Watson, J, Orfi, L, Tonks, N, Pappin, D
Phospholipase D2 Restores Endothelial Barrier Function by Promoting PTPN14-mediated VE-cadherin Dephosphorylation
23 Apr 2020 | Journal of Biological Chemistry | 295(22):7669-7685
Fu, P, Ramchandran, R, Shaaya, M, Huang, L, Ebenezer, D, Jiang, Y, Komarova, Y, Vogel, S, Malik, A, Minshall, R, Du, G, Tonks, N, Natarajan, V
23 Dec 2019 | Nature Chemical Biology | 16(2):122-125
Londhe, A, Bergeron, A, Curley, S, Zhang, F, Rivera, K, Kannan, A, Coulis, G, Rizvi, S, Kim, S, Pappin, D, Tonks, N, Linhardt, R, Boivin, B
1 Jul 2018 | Genes and Development | 32(13-14):944-952
Krishnan, N, Felice, C, Rivera, K, Pappin, D, Tonks, N
Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER
18 Jun 2018 | Cellular Signalling | 50:100-110
Zhang, Jiali, Wang, Zuo, Zhang, Siwei, Chen, Yanxun, Xiong, Xuexue, Li, Xiaojuan, Tonks, Nicholas, Fan, Gaofeng
A potent, selective and orally bioavailable inhibitor of the protein tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models
2 Feb 2018 | Journal of Biological Chemistry | 293(5):1517-1525
Krishnan, N, Konidaris, K, Gasser, G, Tonks, N
18 Jan 2018 | Nature Communications | 9(1):283
Krishnan, N, Bonham, C, Rus, I, Shrestha, O, Gauss, C, Haque, A, Tocilj, A, Joshua-Tor, L, Tonks, N