A5047729222- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Medical Imaging and Pathology Studies
- Cancer Genomics and Diagnostics
- T-cell and Retrovirus Studies
- Advanced biosensing and bioanalysis techniques
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Wnt/β-catenin signaling in development and cancer
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Childhood Cancer Survivors' Quality of Life
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
Beckman Research Institute
2018-2024
Peter MacCallum Cancer Centre
2021-2024
The University of Melbourne
2021-2024
City of Hope
2018-2024
Yale Cancer Center
2020-2021
Yale University
2020-2021
South Australian Health and Medical Research Institute
2014-2018
California Library Association
2018
The University of Adelaide
2011-2017
Centre for Cancer Biology
2011-2017
In cancer, fusions are important diagnostic markers and targets for therapy. Long-read transcriptome sequencing allows the discovery of with their full-length isoform structure. However, due to higher error rates, fusion finding algorithms designed short reads do not work. Here we present JAFFAL, identify from long-read sequencing. We validate JAFFAL using simulations, cell lines, patient data Nanopore PacBio. apply single-cell find spanning three genes demonstrating transcripts detected...
Oncogenic gene fusions are key drivers of cancer, yet most remain untargetable by current therapies. Here, we establish CRISPR-PspCas13b as a personalizable platform for systematic silencing various fusion transcripts. We reveal that recognition and cleavage the breakpoint sequence PspCas13b disrupts transcript, resulting in unexpected RNA nicking ligation near site, which generates out-of-frame, translation-incompetent This approach efficiently degrades canonical drug-resistant BCR::ABL1...
Zinc-finger protein 384 (ZNF384) fusions are an emerging subtype of precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL) and here we further characterised their prevalence, survival outcomes transcriptome.Bone marrow mononuclear cells from 274 BCR-ABL1-negative pre-B-ALL patients were immunophenotyped transcriptome molecularly characterised. Transcriptomic data was analysed by principal component analysis gene-set enrichment to identify gene pathway expression changes.We exclusively...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with median survival of 14 months (with window 6–28 months) from diagnosis.1 BPDCN derived the precursors cells2 recognized as an independent entity myeloid neoplasms in 2016 updated World Health Organization classification.3 Although predominantly affects adults age 70s, cases involving younger children have been reported. Unique clinical presentations include skin infiltration, at...
ABSTRACT Aberrant activation of β-catenin is a common event in AML and an independent predictor poor prognosis. Although increased signaling has been associated with oncogenic translocation products activating mutations the FLT3R, mechanisms that activate more broadly are still unclear. Here, we describe novel link between IL-3 regulation myeloid transformation AML. In murine model HoxB8 cooperation, show protein levels modulated by Cre-induced deletion abolishes IL-3-dependent growth colony...
Significance B lymphoid transcription factors (e.g., IKZF1 and PAX5) not only mediate cell lineage commitment but also repress glucose transport energy supply, thus acting as metabolic gatekeepers. While previous studies showed regulation of gatekeeper functions at the transcriptional level, we here discovered a mechanism based on protein–protein interactions between PON2 glucose-transport inhibitor stomatin (STOM).
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL characterized by gene expression profile resembling Philadelphia chromosome-positive (Ph+ ALL) in the absence BCR-ABL1. Tyrosine kinase-activating fusions, some involving ABL1, are recurrent drivers Ph-like and targetable with tyrosine kinase inhibitors (TKIs). We identified rare instance SFPQ-ABL1 child ALL. expressed cytokine-dependent cell lines was sufficient to transform cells these were...
<title>Abstract</title> B-cell receptor (BCR) signaling plays an important role in the pathogenesis of mantle cell lymphoma (MCL), but detailed mechanisms are not fully understood. In this study, through a genome-wide loss-of-function screen, we have identified carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) as essential factor subset MCL tumors. Our BCR signal transduction studies revealed that CEACAM1 critical by orchestrating two dynamic processes. First, following...
Single-nucleotide variants (SNVs) are extremely prevalent in human cancers, although most of these remain clinically unactionable. The programmable RNA nuclease CRISPR-Cas13 has been deployed to specifically target oncogenic RNAs. However, silencing SNVs with single-base precision remains challenging due the intrinsic mismatch tolerance Cas13. Here, we show that introducing synthetic mismatches at precise positions spacer sequence enables de novo design guide RNAs [CRISPR (crRNAs)] strong...
Abstract Massively parallel short read transcriptome sequencing has greatly expanded our knowledge of fusion genes which are drivers tumor initiation and progression. In cancer, many fusions also important diagnostic markers targets for therapy. Long allows the full length transcripts to be discovered, however, this data a high rate errors finding algorithms designed reads do not work. While numerous now exist RNA data, there few methods detect using third generation or long data. Fusion in...