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:
My group has been set up to encompass a very broad technology base, bringing together expertise in:
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.
Switzerland, University of Basel, PhD
Switzerland, University of Basel, MSc
2023 Fellow of the American Association of Cancer Research (AACR)
2019 CSL Florey Medal, with David Vaux
2016 Fellow of the Australian Academy of Health and Medical Sciences
2016 ECDO Career Award for Excellence in Cell Death Research
2016 Fellow, Australian Academy of Medical & Health Sciences
2014 Einstein Award of the Chinese Academy of Science
2011 Victoria Prize
2009 Associate (Foreign) Member of the European Molecular Biology Organisation
2003-2021 Program Grants, National Health and Medical Research Council (CIA since 2017)
2001-2022 Specialized Center of Research Grants, Leukemia & Lymphoma Society
2002-2021 Research Fellowships (Senior Professional Research Fellow), National Health and Medical Research Council
2022-2026 Investigator grant, National Health and Medical Research Council
2022-2026 Synergy grant, National Health and Medical Research Council
2023-2026 Venture Grant, Cancer Council Victoria
Advisory Board, Faculty of 1000 Medical Research and Biology
Co-Organiser, EMBO Workshops on Animal Models in Cell Death Research and Cancer, Obergurgl, Austria, 2009, 2011, 2013
Associate Editor for J Exp Med, Genes to Cells, Cell Death Differ, Int J Mol Med, Curr Opin Immunol, and J Cell Biol
Doerflinger M, Deng Y, Whitney P, Salvamoser R, Engel S, Kueh A, Tai L, Bachem A, Gressier E, Wilcox E, Geoghegan N, Rogers K, Garnham A, Dengler M, Bader SM, Ebert G, Pearson J, DeNardo D, Wang N, Yang C, Pereira M, Bryant C, Strugnell R, Vince J, Pellegrini M, Strasser A*, Bedoui S*, Herold M* (* joint senior authors). Flexible usage and interconnectivity of diverse cell death pathways protects against intracellular infection. Immunity, 53, 533-547, 2020.
Aubrey BJ, Janic A, Chen Y, Chang C, Lieschke EC, Diepstraten ST, Kueh AJ, Bernardini JP, Dewson G, O’Reilly LA, Whitehead L, Voss AK, Smyth GK, Strasser A*, Kelly GL*. (* joint senior authors). Mutant TRP53 exerts a target gene selective dominant negative effect to drive tumor development. Genes Dev, 32, 1420-1429, 2018.
Ke F*, Vanyai H*, Cowan A, Whitehead L, Delbridge ARD, Grabow S, Czabotar P, Voss AK#, Strasser A#. (* joint first authorship; # joint senior authorship). Embryogenesis and adult life in the absence of intrinsic apoptosis effectors BAX, BAK and BOK. Cell, 173, 1217-1230, 2018.
Janic A, Valente LJ, Wakefield MJ, Di Stefano L, Milla L, Wilcox S, Yang H, Tai L, Vandenberg CJ, Kueh AJ, Mizutani S, Brennan MS, Schenk RL, Lindqvist LM, Papenfuss AT, O’Connor L*, Strasser A*#, Herold MJ*. (these authors share senior authorship; # corresponding author). DNA repair processes are critical mediators of p53-dependent tumour suppression. Nature Medicine, 24, 947-953, 2018.
Kotschy A, Szlavik Z, Murray J, Davidson J, Maragno AL, Le Toumelin-Braizat G, Chanrion M, Kely GL, Gong J, Moujalled D, Bruno A, Csekei M, Paczal A, Szabo Z, Sipos S, Radics G, Proszenyak A, Balint B, Ondi L, Blasko G, Robertson A, Surgenor A, Dukorno P, Chen I, Matassova N, Smith J, Pedder C, Graham C, Studeny A, Lysiak-Auvity G, Girard A-M, Grave F, Segal D, Riffkin CD, Pomilio G, Brennan MS, Herold MJ, Chang C, Guasconi G, Cauquil N, Melchiore F, Guigal-Stephan N, Lockhart B, Colland F, Hickman JA, Roberts AW, Huang DCS, Wei A, Strasser A, Lessene G, Geneste O. Potent and selective MCL1 inhibition is tolerable and efficacious in multiple cancer models. Nature. 2016 Oct 27;538(7626):477-482. PMID: 27760111.
Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J, Strasser A, Kaufmann T. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature. 2009 Aug 20;460(7258):1035-9. PMID: 19626005.
Puthalakath H, O’Reilly LA, Gunn P, Lee L, Kelly PN, Huntington ND, Hughes PD, Michalak EM, McKimm-Breschkin J, Motoyama N, Gotoh T, Akira S, Bouillet P, Strasser A. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell. 2007 Jun 29;129(7):1337-49. PMID: 17604722.
Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JM, Strasser A. p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science. 2003 Nov 7;302(5647):1036-8. PMID: 14500851.
Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Kontgen F, Adams JM, Strasser A. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science. 1999 Nov 26;286(5445):1735-8. PMID: 10576740.
Strasser A, Harris AW, Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889-99. PMID: 1959134.
Strasser A, Whittingham S, Vaux DL, Bath ML, Adams JM, Cory S, Harris AW. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci USA. 1991 Oct 1;88(19):8661-5. PMID: 1924327.
Strasser A, Harris AW, Bath ML, Cory S. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990 Nov 22;348(6299):331-3. PMID: 2250704.
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.
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).
Team members: Zilu Wang, Elizabeth Lieschke, Annabella Thomas, Lois Kerswell, Shuai Huang; in close collaboration with the labs of Gemma Kelly, Kate Sutherland and Tracy Putoczki
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.
Team members: Kerstin Brinkmann, Annli Tee, Leonie Gibson; in collaboration with the Gemma Kelly and Marco Herold labs
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.
Team members: Diane Moujalled, Eiman Saleh