Dickins Group - AML

Group Leader
Ross Dickins 2018
A/Prof Ross Dickins (PhD)

Research Fellow
Dr Katharine Goodall (PhD)

Research Assistant
Mr Max Garwood  BSc(Hons)

PhD Students
Mr Steven Ngo BSc(Hons)
Mr Ethan Oxley BBiotech(Hons)

Honours Students
Mr Ariel Lebenbaum 
Ms Jacqueline Rusnak

Key terms

Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Tumour suppressor genes, Transcription factors, Differentiation therapy

2019 Dickins group
2019 group (L-R): Dr Katharine Goodall, Mr Max Garwood, Mr Ethan Oxley, Ms Jacqueline Rusnak, A/Prof Ross Dickins, Mr Ariel Lebenbaum, Mr Steven Ngo.

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.

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) and acute lymphoblastic leukemia (ALL) are caused by genetic mutations that block the maturation of white blood cell progenitors, locking them in a state of perpetual proliferation. Our laboratory examines how driver mutations contribute to the maturation block in acute leukemia. We aim to develop 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. These tools uncover how particular mutations promote leukemia growth and therapy resistance, and gene products critical for leukemia maintenance.

Funding

Our laboratory is funded by the Australian Government National Health and Medical Research Council (NHMRC), and previously by the Leukaemia Foundation of Australia, the Sylvia and Charles Viertel Charitable Foundation, and veski.

Selected Publications

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

Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Torres Martin M, Guillamot M, Bahn RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I. Cell 170, 1079-1095 (2017).

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).

Variability of inducible expression across the hematopoietic system of tetracycline transactivator transgenic mice. Takiguchi M, Dow LE, Prier JE, Carmichael CL, Kile BT, Turner SJ, Lowe SW, Huang DCS, Dickins RA. PLoS ONE 8, e54009 (2013).

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).

Dickins Lab Alumni

Thao Nguyen, PhD (Postdoc 2018) Research Fellow & Lab Manager, Cartherics

Swathy Jayakrishnan (Hons 2018)

Margherita Ghisi, PhD (Postdoc 2014-2015) Postdoctoral Fellow, Toulouse, France

Tina Vu, BSc(Hons) (Hons 2017) Commerce student

Emilia Simankowicz, BanimalVetBioscience (RA 2015-2018) Research Assistant

Minhee Halemba, BSc(Hons) (RA 2014-2015) PhD student, Monash University

Michael Erlichster, PhD (Hons 2013) Research Scientist, MX3 Diagnostics

Mutlu Kartal-Kaess, MD PhD (Postdoc 2010-2013) Medical Specialist, Heidelberg, Germany

Matthew Witkowski, PhD (Hons 2011, PhD 2012-2015) Postdoctoral Fellow, NYU, USA

Mark McKenzie, PhD (Postdoc 2010-2015) Postdoctoral Fellow, WEHI

Laura Tuohey, BMS/BBT (RA 2010-2011) Research Assistant, Royal Melbourne Hospital

Luisa Cimmino, PhD (Postdoc 2008-2011) Lab Head, University of Miami, USA

Megumi Takiguchi, PhD (Postdoc 2009-2012) Dentist, Perth

Grace Liu, PhD (PhD 2010-2014) Postdoctoral Fellow, IMP, Vienna

Rachael Lane (RA 2008-2012) Research Assistant, Monash University

Sarah Best, PhD (RA 2008, Hons 2009) Postdoctoral Fellow, WEHI