Dickins Group - AML
Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Tumour suppressor genes, Transcription factors, Differentiation therapy
2020 group L-R: Mr Max Garwood, Ms Jade Jowett-Crociani, Dr Katharine Goodall, A/Prof Ross Dickins, Dr Steven Ngo, Mr Ethan Oxley, Ms Skye Ho.
Group Leader - A/Prof Ross Dickins (PhD)
As a postdoctoral scientist in New York, A/Prof Ross Dickins helped develop RNA interference technology allowing reversible inhibition of endogenous gene expression in cultured cells and in mice. His laboratory now uses these tools to investigate hematopoiesis and leukemia, focusing on genes recurrently mutated in acute myeloid leukemia (AML).
Find out more about A/Prof Ross Dickins
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.
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 progenitor maturation, locking them 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.
Our laboratory is funded by the Australian Government National Health and Medical Research Council and the Mark Foundation for Cancer Research. Previously we have received funding from the Leukaemia Foundation of Australia, the Sylvia and Charles Viertel Charitable Foundation, veski, and Australian Rotary Health.
- See more of Ross's publications on his Monash University Staff Profile
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
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).
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
Steven Ngo (PhD 2016-19, Postdoc 2019-21) London, UK
Skye Ho (Hons 2020) Melbourne
Jade Jowett-Crociani (Hons 2020) Melbourne
Ariel Lebenbaum (Hons 2019) Melbourne
Jacqueline Rusnak (Hons 2019) Melbourne
Thao Nguyen (Postdoc 2018) Melbourne
Swathy Jayakrishnan (Hons 2018) Rome, Italy
Margherita Ghisi (Postdoc 2014-15) Toulouse, France
Tina Vu (Hons 2017) Sydney
Emilia Simankowicz (RA 2015-18) Melbourne
Minhee Halemba (RA 2014-15) Melbourne
Michael Erlichster (Hons 2013) Melbourne
Mutlu Kartal-Kaess (Postdoc 2010-13) Bern, Switzerland
Matthew Witkowski (Hons 2011, PhD 2012-15) Aurora, Colorado
Mark McKenzie (Postdoc 2010-15) Melbourne
Laura Tuohey (RA 2010-11) Melbourne
Luisa Cimmino (Postdoc 2008-11) Miami, Florida
Megumi Takiguchi (Postdoc 2009-12) Perth
Grace Liu (PhD 2010-14) Vienna, Austria
Rachael Lane (RA 2008-12) Melbourne
Sarah Best (RA 2008, Hons 2009) Melbourne