A5034425905- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Viral-associated cancers and disorders
- Cell death mechanisms and regulation
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Cutaneous lymphoproliferative disorders research
- Multiple Myeloma Research and Treatments
- Cancer Mechanisms and Therapy
- Cell Adhesion Molecules Research
- Fungal Infections and Studies
- Platelet Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Nanoparticle-Based Drug Delivery
- RNA and protein synthesis mechanisms
- Hematopoietic Stem Cell Transplantation
- Glycosylation and Glycoproteins Research
- RNA Research and Splicing
- Lymphoma Diagnosis and Treatment
- MicroRNA in disease regulation
- Virus-based gene therapy research
- Acute Lymphoblastic Leukemia research
Karolinska Institutet
2022-2024
Walter and Eliza Hall Institute of Medical Research
2014-2024
The University of Melbourne
2015-2023
The CRISPR/Cas9 technology enables the introduction of genomic alterations into almost any organism; however, systems for efficient and inducible gene modification have been lacking, especially deletion essential genes. Here, we describe a drug-inducible small guide RNA (sgRNA) vector system allowing ubiquitous in murine human cells. This mediates efficient, temporally controlled MCL-1, both vitro vivo, Burkitt lymphoma cell lines that require this anti-apoptotic BCL-2 protein sustained...
Abstract Rare multipotent stem cells replenish millions of blood per second through a time-consuming process, passing multiple stages increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight need for more rapid replenishment from cells, established models hematopoiesis implicate only one mandatory differentiation pathway each cell lineage. Here, we establish nonhierarchical relationship between distinct that all lineages and almost exclusively...
Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles diverse TP53-activated in suppression remains poorly understood. Knockdown ZMAT3, an RNA-binding zinc-finger protein involved regulating alternative splicing, haematopoietic cells by shRNA caused leukaemia only with concomitant absence PUMA and p21, critical effectors TRP53-mediated apoptosis cell cycle arrest respectively. We were interested to further investigate role ZMAT3 beyond...
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 TP53 is a critical tumor suppressor that mutated in approximately 50% of human cancers. Unveiling the downstream target genes fulfill its function an area intense investigation. Zmat3 (also known as Wig-1 or PAG608 ) one such p53, whose loss hemopoietic stem cells lacking apoptosis and cell cycle regulators, Puma p21, respectively, promotes development leukemia. The tumorigenesis however remains unclear. Here, to investigate which oncogenic drivers co-operate with promote neoplastic...
Key Points A novel KMT2A-rearrangement, MLL-TFE3, was identified in an infant leukemia patient. MLL-TFE3 expression produces aggressive a mouse model.
SUMMARY MCL-1 is a pro-survival BCL-2 protein required for the sustained growth of many cancers. Recently highly specific MCL-1-inhibitor, S63845, showing 6-fold higher affinity to human compared mouse has been described. To accurately test efficacy and tolerability this BH3 mimetic drug in pre-clinical cancer models, we developed humanized Mcl-1 (huMcl-1) which was replaced with its homologue. HuMcl-1 mice are phenotypically indistinguishable from wild-type but more sensitive inhibition....
Abstract Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles many TP53-activated in suppression remains poorly understood. Knockdown ZMAT3 haematopoietic stem/progenitor cells by shRNA caused leukaemia only with concomitant absence pro-apoptotic BCL-2 family member PUMA and CDK inhibitor p21. We were interested to further investigate role beyond system. Therefore, we generated Zmat3 knockout compound gene mice, lacking p21 , Puma or...