Dickins Group - AML and Immunotherapy

Key terms

Acute myeloid leukaemia, Transcription factors, Differentiation therapy,  Autoimmunity, Inflammation, T cells, Immunotherapy.

Dickins group
2023 group L-R: Back - Zahra Taylor, Ethan Oxley, Veronica Voo, Stephanie Wiranata, Ross Dickins. Front - Jake Tremewen, Samin Iranfar, Imogen Bishop

Group Leader

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Research Overview

The Dickins laboratory at the Australian Centre for Blood Diseases examines what causes leukaemia and how its treatment may be improved. In collaboration with scientific and clinical colleagues at ACBD, across Melbourne, and worldwide, we build and analyse new models of leukemia development and therapy. We aim to understand how recurrent oncogenic mutations influence the behaviour of normal and malignant cells, and how these changes in leukaemia cells may be exploited to therapeutic advantage. We also study how myeloid lineage antigen-presenting cells regulate T cell costimulation in autoimmunity and cancer.

Research Interests

The body produces over 100 billion white blood cells daily, requiring massive proliferation of immature progenitor cells in the bone marrow. Acute myeloid leukemia (AML) is caused by genetic mutations that block progenitor maturation, locking in a state of perpetual proliferation. Our laboratory examines therapeutic strategies that re-engage leukemia cell differentiation and natural mechanisms of mature cell clearance. We use reversible RNAi, CRISPR, and other genetic technologies to generate custom leukemia models that recapitulate the genetics of human leukemia, and test novel therapeutic strategies in established leukemias in mice. We also develop immunomodulatory therapies that activate/suppress T cells in cancer/autoimmune disease.

Funding

Our laboratory is funded by the Australian Government National Health and Medical Research Council, the Mark Foundation for Cancer Research, and the Morgan Mansell Fund. We have previously received funding from CUREator, the Leukaemia Foundation of Australia, the Sylvia and Charles Viertel Charitable Foundation, veski, and Australian Rotary Health.

Dickins Lab Alumni

Selected Publications

Context-restricted PD-(L)1 checkpoint agonism by CTLA4-Ig therapies inhibits T cell activity. Oxley EP*, Kershaw NJ*, Louis C, Goodall KJ, Garwood MM, Jee Ho SM, Voo VTF, Park HY, Iaria J, Wong LLL, Lebenbaum AG, Wiranata S, Pang ES, Edwards ESJ, D'Silva DB, Hansen J, van Zelm MC, O'Keeffe M, Hogarth PM, Haynes NM, Huntington ND, Wicks IP, Dickins RA. Cell Reports 43, 114834 (2024).

Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy. Ngo S, Oxley EP, Ghisi M, Garwood MM, McKenzie MD, Mitchell HL, Kanellakis P, Susanto O, Hickey MJ, Perkins AC, Kile BT, Dickins RA. Nat Commun 12, 6546 (2021).

Interconversion between tumorigenic and differentiated states in acute myeloid leukemia. McKenzie MD*, Ghisi M*, Oxley EP*, Ngo S, Cimmino L, Esnault C, Liu R, Salmon JM, Bell CC, Ahmed N, Erlichster M, Witkowski MT, Liu GJ, Chopin M, Dakic A, Simankowicz E, Pomilio G, Vu T, Krsmanovic P, Su S, Tian L, Baldwin TM, Zalcenstein DA, DiRago L, Wang S, Metcalf D, Johnstone RW, Croker BA, Lancaster GI, Murphy AJ, Naik SH, Nutt SL, Pospisil V, Schroeder T, Wall M, Dawson MA, Wei AH, De The H, Ritchie ME, Zuber J, Dickins RA. Cell Stem Cell 25, 258-272 (2019). *equal contributors

Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome. Witkowski MT, Hu Y, Roberts KG, Boer JM, McKenzie MD, Liu GJ, Le Grice OD, Tremblay CS, Ghisi M, Willson TA, Horstmann MA, Aifantis I, Cimmino L, Frietze S, den Boer ML, Mullighan CG, Smyth GK, Dickins RA. J Exp Med 214, 773-791 (2017).

Activated Notch signaling counteracts Ikaros tumor suppression in mouse and human T cell acute lymphoblastic leukemia. Witkowski MT*, Cimmino L*, Hu Y, Trimarchi T, Tagoh H, McKenzie MD, Best SA, Tuohey L, Willson TA, Nutt SL, Busslinger M, Aifantis I, Smyth GK, Dickins RA. Leukemia 29, 1301-1311 (2015). *equal contributors

Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia. Liu GJ, Cimmino L, Jude JG, Hu Y, Witkowski MT, McKenzie MD, Kartal-Kaess M, Best SA, Tuohey L, Mullighan CG, Farrar MA, Nutt SL, Smyth GK, Zuber J, Dickins RA. Genes Dev 28, 1337-1350 (2014).

Tissue-specific and reversible RNA interference in transgenic mice. Dickins RA, McJunkin K, Hernando E, Premsrirut PK, Krizhanovsky V, Burgess DJ, Kim SY, Cordon-Cardo C, Zender L, Hannon GJ, Lowe SW. Nat Genet 39, 914-921 (2007).

Probing tumor phenotypes using stable and regulated synthetic microRNA precursors. Dickins RA, Hemann MT, Zilfou JT, Simpson DR, Ibarra I, Hannon GJ, Lowe SW. Nat Genet 37, 1289-1295 (2005).

Recent publications