Leukaemia Modelling and Therapeutic Discovery
Research Group Head
Acute Myeloid Leukaemia (AML) is the leading cause of leukaemia-related deaths, with a five-year survival rate of less than 30 per cent. The Carmichael group study the mechanisms driving AML development with the goal of identifying and developing new treatments for this devastating disease.
Overview
Acute Myeloid Leukaemia (AML) is an aggressive blood cancer resulting from the uncontrolled proliferation and impaired function of immature myeloid cells in the bone marrow.
Each year about 1000 Australians are diagnosed with AML and more than half ultimately succumb to their disease within five years. Chemotherapy remains the backbone of AML treatment, and while most patients initially achieve remission with chemotherapy, many will ultimately relapse with chemo-resistant disease. New therapeutic strategies are needed.
The Leukaemia Modelling and Therapeutic Discovery Research group uses sophisticated leukaemia modelling approaches to identify common molecular and biological dependencies of transformed myeloid cells that could offer new therapeutic targets with broad applicability across diverse genetic subtypes.
The ultimate goal of this research is to identify and develop new treatment opportunities for AML patients that will enhance survival and reduce the impact of this aggressive blood cancer on patients, carers and family members.
“AML is a devastating disease with poor survival. Despite decades of research, treatment options remain limited and long-term remission rates low. Only through a deeper understanding of how AML develops can we hope to identify critical dependencies that can be therapeutically exploited to specifically and sensitively kill leukaemia cells.” Dr Catherine Carmichael
Areas of focus
- Investigation of transcription factor function during normal and malignant blood cell development
- Generation of genetic models of Acute Myeloid Leukaemia (AML)
- Targeting Epithelial-Mesenchymal Transition (EMT) modulators in AML
- Generating sophisticated models of childhood AML for the identification of new therapeutic targets
Collaborators
| Dr Jessica Holien | RMIT | Melbourne | Australia |
| Professor Jake Shortt | Monash Health and Monash University | Melbourne | Australia |
| Dr Paul Yeh | Monash Health and Monash University | Melbourne | Australia |
| Professor Andrew Perkins | Australian Centre for Blood Diseases, Monash University | Melbourne | Australia |
| Professor Andrew Wei | WEHI | Melbourne | Australia |
| Professor Hamish Scott | Centre for Cancer Biology | Adelaide | Australia |
Our research focus
Research Group
Dr Karthika Radhakrishnan, Postdoctoral Scientist
Steve Lin, Research Assistant, Research Support Staff
Lynda Truong, Research Assistant, Research Support Staff
Janette Vanessa, Visiting Masters student, Visiting Scholar
Jiarna Zerella, Visiting PhD student, Visiting Scholar
Selected publications
Carmichael CL, Wang J, Nguyen T, Kolawole O, Benyoucef A, De Mazière C, Milne AR, Samuel S, Gillinder K, Hediyeh-Zadeh S, Vo ANQ, Huang Y, Knezevic K, McInnes WRL, Shields BJ, Mitchell H, Ritchie ME, Lammens T, Lintermans B, Van Vlierberghe P, Wong NC, Haigh K, Thoms JAI, Toulmin E, Curtis DJ, Oxley EP, Dickins RA, Beck D, Perkins A, McCormack MP, Davis MJ, Berx G, Zuber J, Pimanda JE, Kile BT, Goossens S, Haigh JJ (2020) The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1. Blood, 136:957-973.
Fagnan A, Bagger FO, Piqué-Borràs MR, Ignacimouttou C, Caulier A, Lopez CK, Robert E, Uzan B, Gelsi-Boyer V, Aid Z, Thirant C, Moll U, Tauchmann S, Kurtovic-Kozaric A, Maciejewski J, Dierks C, Spinelli O, Salmoiraghi S, Pabst T, Shimoda K, Deleuze V, Lapillonne H, Sweeney C, De Mas V, Leite B, Kadri Z, Malinge S, de Botton S, Micol JB, Kile B, Carmichael CL, Iacobucci I, Mullighan CG, Carroll M, Valent P, Bernard OA, Delabesse E, Vyas P, Birnbaum D, Anguita E, Garçon L, Soler E, Schwaller J, Mercher T (2020) Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers. Blood, 136:698-714.
Iacobucci I, Wen J, Meggendorfer M, Choi JK, Shi L, Pounds SB, Carmichael CL, Masih KE, Morris SM, Lindsley RC, Janke LJ, Alexander TB, Song G, Qu C, Li Y, Payne-Turner D, Tomizawa D, Kiyokawa N, Valentine M, Valentine V, Basso G, Locatelli F, Enemark EJ, Kham SKY, Yeoh AEJ, Ma X, Zhou X, Sioson E, Rusch M, Ries RE, Stieglitz E, Hunger SP, Wei AH, To LB, Lewis ID, D’Andrea RJ, Kile BT, Brown AL, Scott HS, Hahn CN, Marlton P, Pei D, Cheng C, Loh ML, Ebert BL, Meshinchi S, Haferlach T, Mullighan CG (2019) Genomic subtyping and therapeutic targeting of acute erythroleukemia. Nat Genet, 51:694-704.
Thirant C, Ignacimouttou C, Lopez CK, Diop M, Le Mouël L, Thiollier C, Siret A, Dessen P, Aid Z, Rivière J, Rameau P, Lefebvre C, Khaled M, Leverger G, Ballerini P, Petit A, Raslova H, Carmichael CL, Kile BT, Soler E, Crispino JD, Wichmann C, Pflumio F, Schwaller J, Vainchenker W, Lobry C, Droin N, Bernard OA, Malinge S, Mercher T (2017) ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia. Cancer Cell, 31:452-465.
Tang JZ, Carmichael CL, Shi W, Metcalf D, Ng AP, Hyland CD, Jenkins NA, Copeland NG, Howell VM, Zhao ZJ, Smyth GK, Kile BT, Alexander WS (2013) Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia. Proc Natl Acad Sci U S A, 110:6091-6096.
Carmichael CL, Metcalf D, Henley KJ, Kruse EA, Di Rago L, Mifsud S, Alexander WS, Kile BT (2012) Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythro-megakaryocytic leukemia. Proc Natl Acad Sci U S A, 109:15437-15442.
Hahn CN, Chong CE*, Carmichael CL*, Wilkins EJ, Brautigan PJ, Li XC, Babic M, Lin M, Carmagnac A, Lee YK, Kok CH, Gagliardi L, Friend KL, Ekert PG, Butcher CM, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Escher R, Bardy PG, Suthers GK, D’Andrea RJ, Horwitz MS, Scott HS (2011) Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet, 43:1012-1017. *Equal contribution.
Ng AP, Hyland CD, Metcalf D, Carmichael CL, Loughran SJ, Di Rago L, Kile BT, Alexander WS (2010) Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome. Blood, 115:3966-3969.
Carmichael CL, Majewski IJ, Alexander WS, Metcalf D, Hilton DJ, Hewitt CA, Scott HS (2009) Hematopoietic defects in the Ts1Cje mouse model of Down syndrome. Blood, 113:1929-1937.
