Cancer |
We are a molecular and cell biology laboratory with a research focus in blood development and leukemia. Our research interest lies in identifying critical components of the hematopoietic transcriptional network in healthy and leukemic blood stem cells and how these govern stemness. We explore how this network is perturbed in blood stem disorders such as myelodysplasia (MDS) and acute myeloid leukemia (AML) and the impact of mutations on clonal dominance. We also investigate the role of stromal and immune cells in the development of blood stem cells in the embryo and the maintenance of leukemic cells in patients.Â
Current projects
- COSMOS-AML; Evaluation of Combined Sensitising and Hypomethylating Therapy Outcomes in AML
- Epigenetic reprogramming of chronic myelomonocytic leukaemia cells
- MOSAIC (Modulation of stem cell differentiation in individuals with high-risk clonal haematopoiesis)
- AZA+: A multi-site phase 1/2 dose escalation/expansion trial combining azacitidine and defactinib for high-risk myelodysplastic syndrome patients who fail to respond to azacitidine alone
- Optimising azacitidine responsiveness in myelodysplasia (MDS) and acute myeloid leukaemia (AML)
- The single cell basis for the emergence of drug resistance during Azacitidine therapy in myelodysplastic syndromes and acute myeloid leukemia
- Evaluating in vivo AZA incorporation in mononuclear cells following Vidaza or CC486
- The role of PDGFRA+ stromal cells in directing endothelial to hematopoietic transition during embryonic development
- Ex vivo expansion of mouse and human hematopoietic stem cells
Highlighted publications
- Peter Truong, Sylvie Shen, Swapna Joshi, Md Imtiazul Islam, Ling Zhong, Mark J. Raftery, Ali Afrasiabi, Hamid Alinejad-Rokny, Mary Nguyen, Xiaoheng Zou, Golam Sarower Bhuyan, Chowdhury H. Sarowar, Elaheh S. Ghodousi, Olivia Stonehouse, Sara Mohamed, Cara E. Toscan, Patrick Connerty, Purvi M. Kakadia, Stefan K. Bohlander, Katharine A. Michie, Jonas Larsson, Richard B. Lock, Carl R. Walkley, Julie A. I. Thoms, Christopher J. Jolly, John E. Pimanda; Genome-Wide CRISPR-Cas9 Screening Identifies a Synergy between Hypomethylating Agents and SUMOylation Blockade in MDS/AML. bioRxiv 2024.04.17.589858; (Nature Communications, revisions) doi:Â
- Shruthi Subramanian, Julie A. I. Thoms, Yizhou Huang, Paola Cornejo-Páramo, Forrest C. Koch, Sebastien Jacquelin, Sylvie Shen, Emma Song, Swapna Joshi, Chris Brownlee, Petter S. Woll, Diego Chacon-Fajardo, Dominik Beck, David J. Curtis, Kenneth Yehson, Vicki Antonenas, Tracey O'Brien, Annette Trickett, Jason A. Powell, Ian D. Lewis, Stuart M. Pitson, Maher K. Gandhi, Steven W. Lane, Fatemeh Vafaee, Emily S. Wong, Berthold Göttgens, Hamid Alinejad-Rokny, Jason W. H. Wong, John E. Pimanda; Genome-wide transcription factor–binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs. Blood 2023; 142 (17): 1448–1462. doi:
- Annatina S. Schnegg-Kaufmann, Julie A. I. Thoms, Golam Sarower Bhuyan, Henry R. Hampton, Lachlin Vaughan, Kayleigh Rutherford, Purvi M. Kakadia, Hui Mei Lee, Emma M. V. Johansson, Timothy W. Failes, Greg M. Arndt, Jason Koval, Robert Lindeman, Pauline Warburton, Alba Rodriguez-Meira, Adam J. Mead, Ashwin Unnikrishnan, Sarah Davidson, Mark N. Polizzotto, Mark Hertzberg, Elli Papaemmanuil, Stefan K. Bohlander, Omid R. Faridani, Christopher J. Jolly, Fabio Zanini, John E. Pimanda; Contribution of mutant HSC clones to immature and mature cells in MDS and CMML, and variations with AZA therapy. Blood 2023; 141 (11): 1316–1321. doi:
- Chandrakanthan V, Rorimpandey P, Zanini F, Chacon D, Olivier J, Joshi S, Kang YC, Knezevic K, Huang Y, Qiao Q, Oliver RA, Unnikrishnan A, Carter DR, Lee B, Brownlee C, Power C, Brink R, Mendez-Ferrer S, Enikolopov G, Walsh W, Göttgens B, Taoudi S, Beck D, Pimanda JE. Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta. Nat Cell Biol. 2022 Aug;24(8):1211-1225. doi:
- Thoms JAI, Truong P, Subramanian S, Knezevic K, Harvey G, Huang Y, Seneviratne JA, Carter DR, Joshi S, Skhinas J, Chacon D, Shah A, de Jong I, Beck D, Göttgens B, Larsson J, Wong JWH, Zanini F, Pimanda JE. Disruption of a GATA2-TAL1-ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells. Blood. 2021 Oct 21;138(16):1441-1455. doi:
Our experts
Team members
- Dr Henry Hampton – Postdoctoral Fellow
- Dr Olivia Stonehouse – Postdoctoral Fellow
- Dr Gus Nwosu – Postdoctoral Fellow
- Sarah Davidson – Clinical Trial Program Manager
- Yuvaraj Ghodke – Senior Database Manager
- Griselda Buckland – Senior Trial Manager
- Swapna Joshi – Research Officer
- Sarower Bhuyan – Research Officer
- Forrest Koch – Research Officer
- Mary Nguyen – Research Assistant
- Veena Gullapalli – PhD student
- Elaheh Ghodousi – PhD student
- Jianwen Deng – PhD student
- Xiaoheng Zou – PhD student
Ruchira Dissanayake – PhD student - Nirasha Wickramasinghe – PhD student
Associated academics
- (ANU)
- (Children’s Cancer Institute)
- (Wellcome Sanger Institute)
- (Cambridge Stem Cell Institute)
- (Cleveland Clinic)
- (Mayo Clinic)
- (POWH, UNSW)
- (Hong Kong University, UNSW)
- (Cambridge Stem Cell Institute)
- (University of Oxford)
- (University of Oxford)
- (Schneider Children’s Medical Center of Israel)
- (Karolinska Institute)
- (UNSW)
- (UNSW)
- (UNSW)
- (UNSW)
- (UNSW)
Honor students
- Nethuli Samaranayake – Honours student
- Andy Wang – ILP student
Research Theme