Prof Andreas Strasser, Division Head | WEHI Researcher Profile

Q: Understanding the molecular mechanisms that control cell death in health and disease

We are using genetic (Crispr/Cas9 and shRNA library) screens to identify critical regulators of cell death signalling and tumour suppression by p53. The functions of ‘hits’ from these screens will be identified by generating in vivo laboratory models that lack or over-express these proteins.We expand substantial effort on clinical translation of our discoveries by collaborating with chemists and structural biologists at the institute, and leading biotech/pharma companies from overseas. Most notably this has assisted in development of inhibitors of pro-survival BCL-2 family members (so-called BH3 mimetics) for cancer therapy. Undertaken in close collaboration with the Gemma Kelly and Marco Herold labs.

Q: How does p53 suppress tumour development?

In collaboration with the Kelly and Herold labs we have generated a pair of complementary gene-targeted mice in which we can change cells from a wt p53 into a mutant p53 state and then (strain 1) back into wt p53 or (strain 2) into a p53 deficient state. The analysis of these mice combined with models of lymphoma, lung cancer or pancreatic cancer will inform on how to best develop novel therapeutics to treat cancers driven by mutations in p53 (~50% of human cancers).

Q: Which functions of MCL-1, inhibiting apoptosis or maximising mitochondrial ATP production, are critical for development and organ function in adulthood?

MCL-1 is a well-known anti-apoptotic member of the BCL-2 protein family. It is an attractive therapeutic target for many cancers because genetic removal or drug-mediated inhibition of MCL-1can kill a broad range of malignant cells. We have generated so-called anti-apoptotic BCL-2 family member gene-swap mice to examine which of the two functions of MCL-1 - inhibiting apoptosis or maximising mittochondrial ATP production, is needed for animal development and adult tissue function. The finding from these studies are critical for the clinical development of MCL-1 inhibitors for cancer therapy.

Q: BH3 mimetic therapies for brain cancer

Our laboratory previously identified factors that are critical for the sustained survival and expansion of different types of cancer cells. Collaborations with major pharmaceutical companies facilitated the development of so-called ‘BH3-mimetic’ drugs that inhibit these pro-survival factors, called BCL-2, MCL-1 and BCL-XL. We showed that these BH3 mimetic drugs can efficiently kill a broad range of cancer cells. We have found that in tissue culture ‘BH3-mimetic drugs’ can kill human brain cancer cells much more potently than the currently used chemotherapeutics.With the support of the Cure Brain Cancer Foundation, we have established new models of brain cancer to test and evaluate the potential of BH3-mimetic drugs for the treatment of patients with brain cancer. We are now undertaking pre-clinical studies to test whether these drugs are effective ‘in vivo’. If these studies prove successful, we will engage clinical collaborators to proceed with clinical trials.

About

My research is focused on understanding the molecular mechanisms of apoptosis, with a particular focus on leukaemias and lymphomas. To do this, we use gene-targeting technologies as well as biochemical and molecular biology tools.

This is answering important questions about:

– The regulation of apoptosis and other forms of cell death
– How apoptosis and other forms of cell death are disrupted during development of haematopoietic and epithelial tumours, and autoimmune disease
– The contribution of impaired apoptosis and possibly other forms of cell death to chemoresistance
– How we can manipulate apoptosis and possibly other forms of cell death for therapeutic benefit
– How the tumour suppressor p53 prevents tumour development and how it functions in cancer therapy
– Our long-term ambition is to use this knowledge to develop new approaches to the treatment and prevention of cancer and autoimmune disease.

My group has been set up to encompass a very broad technology base, bringing together expertise in:

– In vivo biology
– Transgenic and gene targeting technology
– Molecular biology, including lentiviral and shRNA vector production as well as CRISPR mediated genome editing in cell lines, primary cells and in mice
– Biochemistry
– Yeast genetics
– Monoclonal antibody production
– Immunology and haematology

This allows us to tackle many important questions in cell death, molecular oncology and immunology and helped to establish our group at the forefront in our area of research.

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Selected publications from Prof Andreas Strasser

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

Lawrence EM, Cooray A, Kueh AJ, Pal M, Tai L, Garnham AL, Li-Wai-Suen CSN, Vanyai H, Gouil Q, Lancaster J, Callegari S, Whelan L, Lieschke E, Thomas A, Strasser A, Liao Y, Shi W, Wei AH, Herold MJ. Transcriptomic changes including p53 dysregulation prime DNMT3A mutant cells for transformation. EMBO Reports. 2025;26(11):10.1038/s44319-025-00450-4

Tee A, Kueh AJ, Gibson L, Malelang S, Herold MJ, Kelly G, Strasser A, Brinkmann K. Abstract 1379: Discovering the essential functions of MCL-1 in hematopoiesis using gene-swap mice. Cancer Research. 2025;85(8_Supplement_1):10.1158/1538-7445.am2025-1379

Gong J-N, Djajawi TM, Moujalled DM, Pomilio G, Khong T, Zhang L-P, Fedele PL, Low MS, Anderson MA, Riffkin CD, White CA, Lan P, Lessene G, Herold MJ, Strasser A, Spencer A, Grigoriadis G, Wei AH, van Delft MF, Roberts AW, Huang DCS. Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins. Cell Death & Differentiation. 2025;:10.1038/s41418-025-01487-7

Croce CM, Vaux D, Strasser A, Opferman JT, Czabotar PE, Fesik SW. The BCL-2 protein family: from discovery to drug development. Cell Death & Differentiation. 2025;:10.1038/s41418-025-01481-z

Chin HS, Cheng J, Hsu SH, Lum GG, Zaldivia MT, Nelameham S, Guo F, Mallavarapu K, Jackling FC, Yang J, Tan JSL, Sampath P, Barker N, Smyth GK, Lindeman GJ, Strasser A, Visvader JE, Chen Y, Chen T, Fu NY. MCL‑1 safeguards activated hair follicle stem cells to enable adult hair regeneration. Nature Communications. 2025;16(1):10.1038/s41467-025-58150-5

M. Bader S, Scherer L, Schaefer J, Cooney JP, Mackiewicz L, Dayton M, Georgy SR, Davidson KC, Allison CC, Herold MJ, Strasser A, Pellegrini M, Doerflinger M. IL-1β drives SARS-CoV-2-induced disease independently of the inflammasome and pyroptosis signalling. Cell Death & Differentiation. 2025;:10.1038/s41418-025-01459-x

Chen T, Ashwood LM, Kondrashova O, Strasser A, Kelly G, Sutherland KD. Breathing new insights into the role of mutant p53 in lung cancer. Oncogene. 2025;44(3):10.1038/s41388-024-03219-6

Luo M-X, Tan T, Trussart M, Poch A, Nguyen TMH, Speed TP, Hicks DG, Bandala-Sanchez E, Peng H, Chappaz S, Slade C, Utzschneider DT, Koldej RM, Ritchie D, Strasser A, Thijssen R, Ritchie ME, Tam CS, Lindeman GJ, Huang DCS, Lew TE, Anderson MA, Roberts AW, Teh CE, Gray DHD. Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia. Blood. 2024;144(26):10.1182/blood.2024024341

La Marca JE, Kelly GL, Strasser A, Diepstraten ST. Don’t fear the reaper: The role of regulated cell death in tumorigenesis and BH3-mimetics for cancer therapy. Developmental Cell. 2024;59(19):10.1016/j.devcel.2024.06.018

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Lab research projects

Understanding the molecular mechanisms that control cell death in health and disease

How does p53 suppress tumour development?

Which functions of MCL-1, inhibiting apoptosis or maximising mitochondrial ATP production, are critical for development and organ function in adulthood?

BH3 mimetic therapies for brain cancer

Student research projects

Decoding how post-transcriptional mechanisms shape chronic T cell activation

Honours/PhD

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Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways

Honours/PhD

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Decoding how post-transcriptional mechanisms shape chronic T cell activation

Honours/PhD

More information

Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways

Honours/PhD

More information

View all student research projects

Prof Andreas Strasser

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