A5006476436- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Trace Elements in Health
- Iron Metabolism and Disorders
- RNA modifications and cancer
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Pluripotent Stem Cells Research
- Cell death mechanisms and regulation
- RNA regulation and disease
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Cancer-related gene regulation
- Quinazolinone synthesis and applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Phagocytosis and Immune Regulation
- Tissue Engineering and Regenerative Medicine
Murdoch Children's Research Institute
2015-2024
The University of Melbourne
2016-2024
Peter MacCallum Cancer Centre
2021-2024
Royal Children's Hospital
2015-2024
McMaster University
2015-2016
Tokyo Institute of Technology
2012-2015
Abstract Therapies that enhance antitumor immunity have altered the natural history of many cancers. Consequently, leveraging nonoverlapping mechanisms to increase immunogenicity cancer cells remains a priority. Using novel enzymatic inhibitor RNA methyltransferase METTL3, we demonstrate global decrease in N6-methyladenosine (m6A) results double-stranded (dsRNA) formation and profound cell-intrinsic interferon response. Through unbiased CRISPR screens, establish dsRNA-sensing signaling are...
Abstract Hematopoietic stem cells (HSCs) derived from human induced pluripotent (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6. Prkdc scid Il2rg tm1Wjl/SzJ Kit W41/W41 mice. guided differentiating iPS cells, as embryoid bodies a culture medium supplemented with retinyl acetate, through HOXA -patterned mesoderm to hemogenic endothelium specified bone...
ABSTRACT Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scaled-up production of kidney cell types vitro. We describe here a modified suspension culture method for the generation micro-organoids from human pluripotent stem cells. Optimisation differentiation conditions allowed formation micro-organoids, each containing six ten nephrons that were surrounded by endothelial stromal...
Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. However, a drug that directly couples targeting of metabolic dependency with the induction death in cancer cells has largely remained elusive. Here we report drug-like small-molecule ironomycin reduces mitochondrial iron load, resulting potent disruption metabolism. Ironomycin promotes recruitment and activation BAX/BAK, but outer membrane permeabilization (MOMP) does not lead to apoptotic...
The ability to reliably express fluorescent reporters or other genes of interest is important for using human pluripotent stem cells (hPSCs) as a platform investigating cell fates and gene function. We describe simple expression system, designated GAPTrap (GT), in which reporter genes, including GFP, mCherry, mTagBFP2, luc2, Gluc, lacZ are inserted into the GAPDH locus hPSCs. Independent clones harboring variations GT vectors expressed remarkably consistent levels gene. Differentiation...
Abstract Aims/hypothesis Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells the pancreas. Progress in understanding cellular and molecular mechanisms underlying human disease has been hampered a dearth appropriate experimental models. We previously reported characterisation islet-infiltrating CD4 + T from deceased organ donor who had type diabetes. Methods Induced pluripotent stem cell (iPSC) lines derived above were differentiated into CD14...
For stem cell-based treatment of neurodegenerative diseases a better understanding key developmental signaling pathways and robust techniques for producing neurons with highest homogeneity are required. In this study, we demonstrate method using N-cadherin-based biomimetic substrate to promote the differentiation mouse embryonic cell (ESC)- induced pluripotent (iPSC)-derived neural progenitor cells (NPCs) without exogenous neuro-inductive signals. We showed that substrate-dependent...
The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used pluripotent stem reporter lines to track the of endothelial and haematopoietic populations in an vitro model yolk-sac development. identified SOX17−CD34+CD43− cells at day 2 blast colony development, as a haemangioblast-like branch point from which SOX17−CD34+CD43+ SOX17+CD34+CD43− endothelium subsequently arose. Most was dependent on RUNX1. Deletion RUNX1 only...
To develop a disease model for the human 'brittle bone' disease, osteogenesis imperfecta, we have used gene editing to produce facsimile of patient heterozygous COL1A1 mutation in an established control iPSC line. The gene-edited line had normal karyotype, expressed pluripotency markers and differentiated into cells representative three embryonic germ layers. This isogenic parental will be use exploring imperfecta mechanisms therapeutic approaches vitro.
// Robin M. Hallett 3 , Cheng Huang 1, Ali Motazedian 3, 6 Stefanie Auf der Mauer 4 Gregory R. Pond 5 John A. Hassell 2, Robert E. Nordon Jonathan S. Draper 1 McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, University, Hamilton, ON L8N 3Z5, Canada 2 Department Pathology Molecular Biochemistry Biomedical Sciences, Graduate Engineering, University New South Wales, Sydney 2052, Australia Oncology, Murdoch Children's The Royal Hospital, Parkville,...
To develop a disease model for the human ‘brittle bone’ disease, osteogenesis imperfecta, we used simultaneous reprogramming and CRISPR-Cas9 genome editing method to produce an iPSC line with heterozygous patient mutation (COL1A1 c. 3936 G>T) along isogenic gene-corrected control line. Both IPSC lines had normal karyotype, expressed pluripotency markers differentiated into cells representative of three embryonic germ layers. This imperfecta mutant will be use in exploring mechanisms...
Abstract The molecular control of cell fate and behaviour is a central theme in biology. Inherent heterogeneity within populations requires that studied at the single-cell level. Time-lapse imaging tracking are powerful technologies for acquiring lifetime data, allowing quantification how cell-intrinsic extrinsic factors fates over time. However, data contain complex features. Competing fates, censoring, possible inter-dependence competing currently present challenges to modelling data. Thus...
<div>Abstract<p>Therapies that enhance antitumor immunity have altered the natural history of many cancers. Consequently, leveraging nonoverlapping mechanisms to increase immunogenicity cancer cells remains a priority. Using novel enzymatic inhibitor RNA methyltransferase METTL3, we demonstrate global decrease in N6-methyladenosine (m6A) results double-stranded (dsRNA) formation and profound cell-intrinsic interferon response. Through unbiased CRISPR screens, establish...
<p>Gene expression changes + pathways</p>
<p>Proliferation + Apoptosis assays</p>
<p>METTL3 KD in B16 cell line</p>
<p>A20 lymphoma model data</p>
<p>Nanopore workflow</p>
<p>Nanopore workflow</p>
<p>METTL3 KD in B16 cell line</p>