The main focus of our laboratory is to define how signal transduction by cytokines can modulate tissue homeostasis, and to understand how deregulation of these signalling pathways can promote numerous diseases, including cancer.

We use cell biology, molecular biology and structural biology techniques to understand how cytokines enable cancers to grow, metastasise and develop resistance to current treatments.

Our goal is to use the knowledge gained to facilitate the development of new therapeutic opportunities.


Selected publications from A/Prof Tracy Putoczki

Chen YH, Zastrow DB, Metcalfe RD, Gartner L, Krause F, Morton CJ, Marwaha S, Fresard L, Huang Y, Zhao C, McCormack C, Bick D, Worthey EA, Eng CM, Gold J, Undiagnosed Diseases Network, Montgomery SB, Fisher PG, Ashley EA, Wheeler MT, Parker MW, Shanmugasundaram V, Putoczki TL, Schmidt-Arras D, Laurence A, Bernstein JA, Griffin MDW, Uhlig HH. Functional and structural analysis of cytokine-selective IL6ST defects that cause recessive hyper-IgE syndrome. J Allergy Clin Immunol. 2021 Aug;148(2):585-598. doi: 10.1016/j.jaci.2021.02.044. Epub 2021 Mar 23. PMID: 33771552

Low JT, Christie M, Ernst M, Dumoutier L, Preaudet A, Ni Y, Griffin MDW, Mielke LA, Strasser A, Putoczki TL#, O’Reilly LA# Loss of NFKB1 Results in Expression of Tumor Necrosis Factor and Activation of Signal Transducer and Activator of Transcription 1 to Promote Gastric Tumorigenesis in Mice. Gastroenterology. 2020 Jun 20:S0016-5085(20)34840-X. doi: 10.1053/j.gastro.2020.06.039. PMID: 32569771

Metcalfe RD, Aizel K, Zlatic CO, Nguyen PM, Morton CJ, Lio DS, Cheng HC, Dobson RCJ, Parker MW, Gooley PR, Putoczki TL#, Griffin MDW# The structure of the extracellular domains of human interleukin 11α receptor reveals mechanisms of cytokine engagement. J Biol Chem. 2020 Jun 12;295(24):8285-8301. doi: 10.1074/jbc.RA119.012351. Epub 2020 Apr 24. PMID: 32332100

Ziegler PK, Bollrath J, Pallangyo CK, Matsutani T, Canli Ö, De Oliveira T, Diamanti MA, Müller N, Gamrekelashvili J, Putoczki T, Horst D, Mankan AK, Öner MG, Müller S, Müller-Höcker J, Kirchner T, Slotta-Huspenina J, Taketo MM, Reinheckel T, Dröse S, Larner AC, Wels WS, Ernst M, Greten TF, Arkan MC, Korn T, Wirth D, Greten FR. Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell. 2018 Jun 28;174(1):88-101.e16. doi: 10.1016/j.cell.2018.05.028. PMID: 29909986

O’Reilly LA, Putoczki TL*, Mielke LA, Low JT, Lin A, Preaudet A, Herold MJ, Yaprianto K, Tai L, Kueh A, Pacini G, Ferrero RL, Gugasyan R, Hu Y, Christie M, Wilcox S, Grumont R, Griffin MDW, O’Connor L, Smyth GK, Ernst M, Waring P, Gerondakis S, Strasser A. Loss of NF-κB1 Causes Gastric Cancer with Aberrant Inflammation and Expression of Immune Checkpoint Regulators in a STAT-1-Dependent Manner. Immunity. 2018 Mar 20;48(3):570-583.e8. doi: 10.1016/j.immuni.2018.03.003. PMID: 29562203 *Joint first author

Poh AR, Love CG, Masson F, Preaudet A, Tsui C, Whitehead L, Monard S, Khakham Y, Burstroem L, Lessene G, Sieber O, Lowell C, Putoczki TL*, O’Donoghue RJJ, Ernst M. Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression. Cancer Cell. 2017 Apr 10;31(4):563-575.e5. doi: 10.1016/j.ccell.2017.03.006. PMID: 28399411 *Joint senior author

Schafer S, Viswanathan S, Widjaja AA, Lim WW, Moreno-Moral A, DeLaughter DM, Ng B, Patone G, Chow K, Khin E, Tan J, Chothani SP, Ye L, Rackham OJL, Ko NSJ, Sahib NE, Pua CJ, Zhen NTG, Xie C, Wang M, Maatz H, Lim S, Saar K, Blachut S, Petretto E, Schmidt S, Putoczki T, Guimarães-Camboa N, Wakimoto H, van Heesch S, Sigmundsson K, Lim SL, Soon JL, Chao VTT, Chua YL, Tan TE, Evans SM, Loh YJ, Jamal MH, Ong KK, Chua KC, Ong BH, Chakaramakkil MJ, Seidman JG, Seidman CE, Hubner N, Sin KYK, Cook SA. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature. 2017 Dec 7;552(7683):110-115. doi: 10.1038/nature24676 PMID: 29160304

Putoczki TL, Dobson RC, Griffin MD. The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6. Acta Crystallogr D Biol Crystallogr. 2014 Sep;70(Pt 9):2277-85. doi: 10.1107/S1399004714012267. PMID: 25195742

Putoczki TL, Thiem S, Loving A, Busuttil RA, Wilson NJ, Ziegler PK, Nguyen PM, Preaudet A, Farid R, Edwards KM, Boglev Y, Luwor RB, Jarnicki A, Horst D, Boussioutas A, Heath JK, Sieber OM, Pleines I, Kile BT, Nash A, Greten FR, McKenzie BS, Ernst M. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer cell. 2013 Aug 12;24(2):257-71. PMID: 23948300

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