A5083239994- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- HER2/EGFR in Cancer Research
- Sperm and Testicular Function
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Growth Hormone and Insulin-like Growth Factors
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Retinoids in leukemia and cellular processes
- Kruppel-like factors research
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Estrogen and related hormone effects
Walter and Eliza Hall Institute of Medical Research
1998-2024
Cancer Genetics (United States)
2014
The Royal Melbourne Hospital
1996-1999
Monash Medical Centre
1998
Monash University
1998
Monash Institute of Medical Research
1998
Research Institute of Molecular Pathology
1993
Proteins of the Bcl-2 family are important regulators apoptosis in many tissues embryo and adult. The recently isolated bcl-w gene encodes a pro-survival member family, which is widely expressed. To explore its physiological role, we have inactivated mouse by homologous recombination. Mice that lack Bcl-w were viable, healthy, normal appearance. Most exhibited typical histology, hematopoiesis was unaffected, presumably due to redundant function with other members. Although female...
The pivotal step on the mitochondrial pathway to apoptosis is permeabilization of outer membrane (MOM) by oligomers B-cell lymphoma-2 (Bcl-2) family members Bak or Bax. However, how they disrupt MOM integrity unknown. A longstanding model that activated and Bax insert two α-helices, α5 α6, as a hairpin across MOM, but recent insights oligomer structures question this model. We have clarified these helices contribute perforation determining that, in oligomers, (like α5) remains part protein...
To elicit apoptosis, BAX metamorphoses from an inert cytosolic monomer into homo-oligomers that permeabilize the mitochondrial outer membrane (MOM). A long-standing puzzle is BH3 domains apparently activate by not only its canonical groove but also a proposed site involving helices α1 and α6. Our mutagenesis studies reveal late steps like oligomerization require activation through probably earlier MOM association. Conversely, or α6 obstruction alanine scanning implicate these early in...
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...
Drugs targeting various pro-survival BCL-2 family members (''BH3 mimetics'') have efficacy in hemopoietic malignancies, but the non-targeted can promote resistance. Pertinently, sensitivity of some tumor cell lines to BH3 mimetic ABT737, which targets BCL-2, BCL-XL, and BCL-W not MCL-1, is enhanced by 2-deoxyglucose (2DG). We found that 2DG augmented apoptosis induced ABT737 3 8 human lines, most strongly pre-B acute lymphocytic leukemia line NALM-6, focus our mechanistic studies. Although...
MCL-1 is an anti-apoptotic member of the BCL-2 protein family that ensures cell survival by blocking intrinsic apoptotic death pathway 1 . unique in being essential for early embryonic development and many types, including cancer cells, which are not affected loss other members 1–4 Non-apoptotic functions controlling mitochondrial ATP production dynamics have been proposed to underlie this requirement 5–9 The relative contributions versus non-apoptotic normal physiology addressed. Here we...
mice lack common lymphoid progenitors (CLPs) but maintain T cell development d Max41 allele results in ectopic GATA6 expression multipotent drives myelopoiesis through promoting PU.
The traditional view of blood cell development is that myeloid cells are derived from the common progenitor (CMP) population and all lymphoid populations, including B cells, T NK plasmacytoid dendritic arise (CLP) population. In unique Max41 transgenic mouse strain, nearly seem diverted into granulocyte lineage. Herein, we show despite ablation CLP compartment in mice, proceeds normally. contrast these mice present with an absence (pDC). Mechanistically, hematopoietic abnormalities result...