A5060566535- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Acute Myeloid Leukemia Research
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Erythrocyte Function and Pathophysiology
- T-cell and B-cell Immunology
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Phagocytosis and Immune Regulation
- Blood disorders and treatments
- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
The University of Melbourne
2012-2025
Walter and Eliza Hall Institute of Medical Research
2012-2025
Heidelberg University
2018-2022
The Alfred Hospital
2020-2022
DKFZ-ZMBH Alliance
2018-2022
German Cancer Research Center
2018-2022
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2018-2022
Monash University
2020-2022
Australian Centre for HIV and Hepatitis Virology Research
2020-2021
Australasian Leukaemia and Lymphoma Group
2020
Abstract Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell metabolic homeostasis largely unknown cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism vivo patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, regulated the fatty acid synthase (FASN)–stearoyl-CoA desaturase (SCD) axis to...
Randomized trials in acute myeloid leukemia (AML) have demonstrated improved survival by the BCL-2 inhibitor venetoclax combined with azacitidine older patients, and clinical are actively exploring role of combination intensive chemotherapy fitter patients AML. As most still develop recurrent disease, understanding relapse mechanisms is needed. We find that 17% relapsing after venetoclax-based therapy for AML acquired inactivating missense or frameshift/nonsense mutations apoptosis effector...
Iron is mostly devoted to the hemoglobinization of erythrocytes for oxygen transport. However, emerging evidence points a broader role metal in hematopoiesis, including formation immune system. availability mammalian cells controlled by iron-regulatory protein 1 (IRP1) and IRP2. We report that global disruption both IRP1 IRP2 adult mice impairs neutrophil development differentiation bone marrow, yielding immature neutrophils with abnormally high glycolytic autophagic activity, resulting...
PURPOSE A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse. METHODS Patients either MRD (≥1 log 10 rise) relapse (blasts 5%-15%) received 600 mg once daily D1-28 plus LDAC D1-10 28-day cycles. The primary objective was response cohort complete remission (CR/CRh/CRi) cohort. RESULTS Forty-eight adults (n = 26) 22) were enrolled. Median age 67 years...
Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, low throughput often results in insufficient read coverage thereby limiting ability to perform calling for specific genes. Here, we developed a single-cell Rapid Capture Hybridization (scRaCH-seq) method that demonstrated high specificity efficiency capturing targeted transcripts using sequencing, allowing an analysis status...
Abstract Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising have been reported sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) 102 (aged 18-65 years) 2:1 to vs placebo (days 4-10) combined induction: idarubicin 12 mg/m2 on days 1 3 either cytarabine...
Many acute myeloid leukaemias (AMLs) express high levels of BCL-2 and MCL-1, especially after therapy. To test the impact these anti-apoptotic proteins on AML development treatment, we used haemopoietic reconstitution to generate MLL-AF9 AMLs expressing or Mcl-1 transgenes. with elevated MCL-1 had a higher proportion mature cells but, like conventional AMLs, were readily transplantable. Short-term cell lines established from multiple primary each genotype tested in vitro for susceptibility...
The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history murine HSCs in label dilution experiments. A recent study proposed that primitive symmetrically divide only four times to then enter permanent quiescence. We observed background fluorescence due leaky H2B-FP expression, occurring all transgenes independent induction,...
Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The chemotherapy and venetoclax in elderly AML trial (CAVEAT) was first to combine intensive newly diagnosed ≥65 years. In this final analysis, 85 (median age 71 years) were followed median of 41.8 months. CAVEAT induction combined cytarabine idarubicin 5 dose levels (50-600 mg) up 14 days. Two additional cohorts explored adjusted-dose (50 mg, 100 posaconazole. well tolerated,...
Residing at the top of hematopoietic hierarchy, long-term stem cells (HSCs) are capable self-renewal and sustained blood cell regeneration. Over past decades, single-cell clonal analyses have revealed substantial functional molecular heterogeneity within this compartment, challenging notion that is inherently tied to balanced, multi-lineage production. However, a cohesive model explains relationships among these diverse HSC states remains elusive. Here, we combined transplantations over...
The transcriptional represser Mnt is a functional antagonist of the proto-oncoprotein Myc. Both and Myc utilise Max as an obligate partner for DNA binding, Myc/Max Mnt/Max complexes compete occupancy at E-box sequences in promoter regions. We have previously shown transgenic mouse models that phenotype kinetics onset haemopoietic tumours varies with level expression. reasoned decrease would increase accelerate Myc-driven tumorigenesis. tested impact reduced three myc mice p53+/− mice. To our...
The transcription factor c-MYC regulates a multiplicity of genes involved in cellular growth, proliferation, metabolism and DNA damage response its overexpression is hallmark many tumours. Since MYC promotes apoptosis under conditions stress, such as limited availability nutrients or cytokines, MYC-driven cells are very much dependent on signals that inhibit cell death. Stress trigger via the pathway regulated by opposing fractions BCL-2 protein family previous genetic studies have shown...
Abstract Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, low throughput often results in insufficient read coverage thereby limiting ability to perform calling for specific genes. Here, we developed a s ingle- c ell Ra pid Capture H ybridization seq uencing (scRaCH-seq) method that demonstrated high specificity efficiency capturing targeted transcripts using sequencing,...
Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging pathways: the ‘extrinsic’ pathway, which is triggered engagement of cell surface ‘death receptors’ such as Fas/APO-1; ‘intrinsic’ diverse cellular stresses, regulated pro-survival pro-apoptotic members Bcl-2 family proteins. Pro-survival Mcl-1, can block activation proteins, Bax Bak, appears for survival maintenance multiple haemopoietic types....