A/Prof Tracy Putoczki, Lab Head | WEHI Researcher Profile

Q: Defining the mechanism of signalling by cytokines

We have specific expertise in Interleukin (IL)-11, a member of the IL-6 family of pleiotropic cytokines. IL-11 signalling is initiated following binding to its membrane bound, cell-type specific receptor, IL-11R. This binary complex engages a transmembrane receptor called GP130, inducing dimerisation and activation of numerous transcription factors, including STAT3. STAT3 has been implicated in the maintenance of a tumour-promoting microenvironment, and persistent STAT3 activation is a feature of many human cancers of both haematopoietic and epithelial origin.We are part of a multi-institutional collaborative project that was the first to solve the structure of the human IL-11 ligand, receptor and the authentic signalling complex. We build on this knowledge to understand the evolution of cytokine signalling, relationships to disease, and to enable therapeutic development.

Q: Examining how cytokines promote tumour growth, invasion and metastasis

A common feature of all tumours is the bi-directional interactions between tumour cells and the stroma, whereby tumour cells can stimulate the inflamed stroma, which in turn can enhance the malignant traits of tumour cells. This self-amplifying feedback loop is fuelled by cytokines. For this reason, the concept of combating tumour progression, through inhibition of growth promoting cytokines present in the tumour microenvironment is becoming of great therapeutic interest.We are combining laboratory models and patient clinical data to understand the role of cytokines in multiple cancers including the brain, colon, lung and pancreatic cancer and how they promote resistance to standard-of-care therapies, targeted therapies and immunotherapies.

Q: Developing new modalities for treatment of inflammatory bowel disease and cancer

Inflammatory bowel disease patients have an increased risk of colorectal cancer (CRC). CRC is the forth most common cause of malignancy worldwide. Alarmingly, the highest incidence rates occur in Australia, where CRC is the second most common cause of cancer-related deaths.We are establishing new laboratory models to characterise novel proteins that are associated with human inflammatory bowel disease and the development of CRC. Our focus is on drug development and stratification of patients for treatment.

Q: Developing truly personalised pre-clinical models of pancreatic cancer for drug development

Together with a team of clinical and scientific collaborators, we have built a personalised treatment platform for pancreatic cancer, consisting of a tissue biobank and an extensive collection of patient-derived organoids (PDOs) and patient-derived xenografts (PDXs). PDOs are small 3-D cell clusters that are generated from biopsies or from surgically resected pancreatic cancers. Our collection covers the full disease spectrum - from early-stage lesions through to metastatic disease. The advantage of PDOs is that they mirror tumour architecture and can be used to test the efficacy of multiple new drugs in parallel. We were the first to generate a pancreatic cancer PDO biobank in Australia (a collaboration between WEHI and the University of Melbourne). We have validated that PDOs are an excellent patient tumour replica, as their response to chemotherapy matches that of the patient from which they were derived.Over the last 40+ years very few new drugs have been approved, yielding little improvement in pancreatic patient outcomes. Our goal is to continue to develop new model systems to empower personalised medicine, enabling screening for new drugs, combinations treatments, and identification of the patients most likely to respond.

About

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.

Education

Grants and funding

Publications

Selected publications from A/Prof Tracy Putoczki

Doggett K, Morgan KJ, Olthof AM, Mieruszynski S, Williams BB, Garnham AL, Milevskiy MJG, Whitehead L, Coates J, Buchert M, O’Donoghue RJJ, Hall TE, Putoczki TL, Ernst M, Sutherland KD, Kanadia RN, Heath JK. Inhibition of the minor spliceosome restricts the growth of a broad spectrum of cancers. EMBO Reports. 2025;:10.1038/s44319-025-00511-8

Brinkmann K, McArthur K, Malelang S, Gibson L, Tee A, Elahee Doomun SN, Rowe CL, Arandjelovic P, Marchingo JM, D’Silva D, Bachem A, Monard S, Whelan LG, Dewson G, Putoczki TL, Bouillet P, Fu NY, Brown KK, Kueh AJ, Wimmer VC, Herold MJ, Thomas T, Voss AK, Strasser A. Relative importance of the anti-apoptotic versus apoptosis-unrelated functions of MCL-1 in vivo. Science. 2025;:10.1126/science.adw1836

Zuiani J, Wu D, Roach M, Putoczki T, Saad M, Martelotto L, Ryan F, Drogemuller C, Perkins G, Coates T. 11-3: UNDERSTANDING HEREDITARY PANCREATITIS: PATIENT ORGANOIDS COMPLLIMENT SPATIAL TRANSCRIPTOMIC ANALYSIS. Transplantation. 2025;109(6S1):10.1097/01.tp.0001123200.36575.64

M. Bader S, Calleja DJ, Devine SM, Kuchel NW, Lu BGC, Wu X, Birkinshaw RW, Bhandari R, Loi K, Volpe R, Khakham Y, Au AE, Blackmore TR, Mackiewicz L, Dayton M, Schaefer J, Scherer L, Stock AT, Cooney JP, Schoffer K, Maluenda A, Kleeman EA, Davidson KC, Allison CC, Ebert G, Chen G, Katneni K, Klemm TA, Nachbur U, Georgy SR, Czabotar PE, Hannan AJ, Putoczki TL, Tanzer M, Pellegrini M, Lechtenberg BC, Charman SA, Call MJ, Mitchell JP, Lowes KN, Lessene G, Doerflinger M, Komander D. A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID. Nature Communications. 2025;16(1):10.1038/s41467-025-57905-4

Sentosa DD, Metcalfe RD, Sims NA, Putoczki TL, Griffin MDW. The structure of the IL‐11 signalling complex provides insight into receptor variants associated with craniosynostosis. The FEBS Journal. 2025;292(3):10.1111/febs.17307

Pires S, Yang W, Louis C, Tran N, Hassan-Zahraee M, Ye Z, Hung KE, Hyde C, Lukin DJ, Scherl EJ, Targan S, Putoczki T, Wicks I, Longman RS. 220 TL1A DRIVES ILC-MEDIATED GRANULOPOIESIS AND COLITIS ASSOCIATED CANCER. Gastroenterology. 2024;166(5):10.1016/s0016-5085(24)00600-0

Dagley LF, Yousef J, Preaudet A, Loving A, Webb AI, Ernst M, Putoczki TL. Identification of Serum Biomarkers to Monitor Therapeutic Response in Intestinal-Type Gastric Cancer. International Journal of Molecular Sciences. 2024;25(6):10.3390/ijms25063129

Low RRJ, Fung KY, Dagley LF, Yousef J, Emery-Corbin SJ, Putoczki TL. Unbiased Quantitative Proteomics of Organoid Models of Pancreatic Cancer. Methods in Molecular Biology. 2024;2823:10.1007/978-1-0716-3922-1_6

Anand S, Nedeva C, Chitti SV, Fonseka P, Kang T, Gangoda L, Tabassum NI, Abdirahman S, Arumugam TV, Putoczki TL, Kumar S, Mathivanan S. The E3 ubiquitin ligase NEDD4 regulates chemoresistance to 5-fluorouracil in colorectal cancer cells by altering JNK signalling. Cell Death & Disease. 2023;14(12):10.1038/s41419-023-06349-z

Metcalfe RD, Hanssen E, Fung KY, Aizel K, Kosasih CC, Zlatic CO, Doughty L, Morton CJ, Leis AP, Parker MW, Gooley PR, Putoczki TL, Griffin MDW. Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant. Nature Communications. 2023;14(1):10.1038/s41467-023-42754-w