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.
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.
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.
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.
- See more of Ross's publications on his Monash University Staff Profile
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
Swathy Jayakrishnan (Hons 2018) Medical Student, Rome, Italy
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