Prof Andreas Strasser, Lab 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.

Education

Grants and funding

Publications

Selected publications from Prof Andreas Strasser

Grabow S, Waring P, Happo L, Cook M, Mason KD, Kelly PN, Strasser A. Correction to: Pharmacological blockade of Bcl-2, Bcl-xL and Bcl-w by the BH3 mimetic ABT-737 has only minor impact on tumour development in p53-deficient mice. Cell Death & Differentiation. 2026;:10.1038/s41418-026-01826-2

Wen L, Saleh E, Strasser A, Moujalled D. ID #807 Harnessing programmed cell death and metabolic vulnerabilities to enhance therapy in medulloblastoma. Neuro-Oncology Pediatrics. 2026;2(Supplement_1):10.1093/neuped/wuag026.336

Diepstraten ST, La Marca JE, Yuan Y, Brown FC, Roberts AW, Wei AH, Kelly GL, Strasser A. Abstract SY35-01: Enhancing BH3 mimetic drug induced killing of malignant cells for cancer therapy. Cancer Research. 2026;86(8_Supplement):10.1158/1538-7445.am2026-sy35-01

Conrad M, Strasser A, Jost PJ, Yuan J, Shao F, Vandenabeele P, Wahida A. Cell death in cancer. Cell. 2026;189(8):10.1016/j.cell.2026.03.024

M. Bader S, Scherer L, Bhandari R, Motyer AJ, Cooney JP, Mackiewicz L, Dayton M, Sheerin D, V. L. Romero D, Schaefer J, Pang J, Chen S, Schoffer K, Wang L, Jin X, Batey D, Yip RKH, Zaman I, Rajasekhar P, Gartner MJ, Wilcox S, Whitehead L, Georgy SR, Maluenda A, Davidson KC, Allison CC, Bowden R, Brinkmann K, Asselin-Labat M-L, Phipson B, Tanzer MC, Herold MJ, Samson AL, Vince JE, Strasser A, Pellegrini M, Doerflinger M. Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection. Nature Communications. 2025;16(1):10.1038/s41467-025-65098-z

Diepstraten S, La Marca J, Yuan Y, Young S, Chang C, Whelan L, Ross A, Fischer K, Litalien V, Brown F, Roberts A, Wei A, Strasser A, Kelly G. 3151 – PUTTING THE STING BACK INTO THERAPY FOR P53 MUTANT BLOOD CANCERS. Experimental Hematology. 2025;151:10.1016/j.exphem.2025.105092

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;389(6764):10.1126/science.adw1836

Potts MA, Mizutani S, Deng Y, Vaidyanathan S, Ting KE, Giner G, Sridhar S, Shenoy G, Liao Y, Diepstraten ST, Kueh AJ, Pal M, Healey G, Tai L, Wang Z, König C, Kaloni D, Whelan L, Milevskiy MJG, Coughlan HD, Pomilio G, Wei AH, Visvader JE, Papenfuss AT, Wilcox S, Jeyasekharan AD, Shi W, Lelliott EJ, Kelly GL, Brown KK, Strasser A, Herold MJ. Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma. Nature Communications. 2025;16(1):10.1038/s41467-025-62615-y

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;32(8):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;32(8):10.1038/s41418-025-01481-z

View all publications

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 the TP53 Protein Interaction Network to Understand Cell Fate Decisions and Provide the Foundation for Developing New Cancer Therapies

Honours/PhD

More information

Decoding the TP53 Protein Interaction Network to Understand Cell Fate Decisions and Provide the Foundation for Developing New Cancer Therapies

Honours/PhD

More information

View all student research projects

Prof Andreas Strasser

Areas

Diseases

Technologies

Divisions

Sections on this page

About

Publications

Lab research projects