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Nicholas Tonks

Nicholas Tonks

Professor
Caryl Boies Professor of Cancer Research
Cancer Center Deputy Director of Operations

Ph.D., University of Dundee, 1985

tonks@cshl.edu | 516-367-8846

Faculty Profile

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.

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All Publications

PTP1B is an intracellular checkpoint that limits T cell and CAR T cell anti-tumor immunity.

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

Connecting copper and cancer: from transition metal signalling to metalloplasia

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

Regulation of PTP1B activation through disruption of redox-complex formation

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

DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson's disease

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

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development

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

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