A5025963601- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Liver physiology and pathology
- Congenital heart defects research
- Esophageal Cancer Research and Treatment
- Mitochondrial Function and Pathology
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Pickering emulsions and particle stabilization
- Polymer Surface Interaction Studies
- Single-cell and spatial transcriptomics
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Tissue Engineering and Regenerative Medicine
- Bone Tissue Engineering Materials
The University of Queensland
2020-2025
Manchester Academic Health Science Centre
2014-2022
University of Manchester
2014-2022
University of Nottingham
2017-2021
Hepatocyte-like cells (HLCs), differentiated from pluripotent stem by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity whether any deficit represents a true fetal state or aberrant differentiation is unclear compounded comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs multiple lineages, using two different protocols, for direct with fresh
Abstract High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis human embryos is limited to pre-implantation stages, since early post-implantation are largely inaccessible. Notwithstanding, we previously suggested conserved principles pig and development. For further insight on pluripotent states lineage delineation, analysed at single cell resolution. Here show progressive segregation inner mass...
Investigations of the human germline and programming are challenging because limited access to embryonic material. However, pig as a model may provide insights into transcriptional network epigenetic reprogramming applicable both species. Here we show that, during pre- early migratory stages, primordial germ cells (PGCs) initiate large-scale epigenomic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and, potentially, base excision repair (BER). There is also...
Esophageal adenocarcinoma (EAC) is one of the most frequent causes cancer death, and yet compared to other common cancers, we know relatively little about molecular composition this tumor type. To further our understanding cancer, have used open chromatin profiling decipher transcriptional regulatory networks that are operational in EAC. We uncovered a transcription factor network usually found primitive intestinal cells during embryonic development, centered on HNF4A GATA6. These factors...
To interrogate the alternative fates of pancreas and liver in earliest stages human organogenesis, we developed laser capture, RNA amplification, computational analysis deep sequencing. Pancreas-enriched gene expression was less conserved between mouse than for liver. The dorsal pancreatic bud enriched components Notch, Wnt, BMP, FGF signaling, almost all genes known to cause agenesis or hypoplasia, over 30 unexplored transcription factors. SOX9 RORA were imputed as key regulators compared...
Human induced pluripotent stem cells (hiPSCs) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity differentiation specific lineage. Characterization transcriptome 11 hiPSC lines showed that activation MIXL1 at early stage correlated with higher efficacy in generating definitive endoderm advancing maturation derivatives. Enforced expression endoderm-inefficient hiPSCs enhanced differentiation, suggesting modulation key drivers...
There is evidence that ATM mutated in ataxia-telangiectasia (A-T) plays a key role protecting against mitochondrial dysfunction, the mechanism for which remains unresolved. We demonstrate here ATM-deficient cells are exquisitely sensitive to nutrient deprivation, can be explained by defective cross talk between endoplasmic reticulum (ER) and mitochondrion. Tethering these two organelles response stress was reduced lacking ATM, consistent with this, Ca2+ release transfer ER mitochondria...
How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark fidelity of stem cell differentiation programming, interpret pathogenicity noncoding variation. Here, we study histone modifications across thirteen tissues during organogenesis. We integrate data with transcription build an overview how differentially regulates alternative fates including by repression. Promoters from nearly 20,000...
Abstract Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double-stranded breaks response to oxidative stress. We show that CRISPR/Cas9-assisted gene correction combined piggyBac (PB) transposon-mediated excision the selection cassette enables seamless restoration alleles in induced pluripotent stem cells from an A-T patient carrying compound heterozygous exonic missense/frameshift mutations, homozygous splicing acceptor...
Human induced pluripotent stem cells (hiPSC) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity differentiation specific lineage. Characterization transcriptome eleven hiPSC lines showed that activation MIXL1 at early stage correlated with higher efficacy in generating definitive endoderm advancing maturation derivatives. Enforced expression endoderm-inefficient hiPSCs enhanced differentiation, suggesting modulation key drivers...
Abstract High-resolution molecular programs delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis human embryos is limited to pre-implantation stages, since early post-implantation are inaccessible. Notwithstanding, we previously suggested conserved principles pig and development. For further insight on pluripotent states lineage delineation, analysed at single cell resolution. Here show progressive segregation inner mass trophectoderm in...
Summary Investigations on the human germline and programming are challenging due to limited access embryonic material. However, pig as a model may provide insight transcriptional network epigenetic reprogramming applicable both species. Here we show that during pre- early migratory stages primordial germ cells (PGCs) initiate large-scale reprogramming, including DNA demethylation involving TET-mediated hydroxylation potentially base excision repair (BER). There is also macroH2A1 depletion...
Abstract Oesophageal adenocarcinoma (OAC) is one of the most frequent causes cancer deaths and yet compared to other common cancers, we know relatively little about molecular composition this tumour type. To further our understanding have used open chromatin profiling decipher transcriptional regulatory networks that are operational in OAC. We uncovered a transcription factor network usually found primitive intestinal cells during embryonic development, centred on HNF4A GATA6. These factors...
How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark fidelity of vitro stem cell differentiation programming, interpret pathogenicity noncoding variation. Here, we studied histone modifications across thirteen tissues during organogenesis. We integrated data with transcription build first overview how differentially regulates alternative fates including by repression. Promoters from...
Ataxia-telangiectasia (A-T) mutated (ATM) plays a central role in the response to DNA double strand breaks (DNA DSB) but there is increasing evidence that it has key protecting against mitochondrial dysfunction, mechanism for which remains unresolved. We demonstrate here A-T cells are also exquisitely sensitive metabolic stress can be explained by defective cross-talk between endoplasmic reticulum (ER) and mitochondrion through mitochondrial–associated membrane (MAM). showed formation of...
Abstract Hepatocytes derived from human pluripotent stem cells (PSCs) hold great promise for modeling liver disease, in vitro hepatotoxicity testing, and future cellular therapy. However, current protocols generate hepatocyte-like (HLCs) that resemble fetal hepatocytes, thus do not accurately recapitulate the molecular identity functions of adult liver. To address this, we compared transcriptomes to PSC-derived HLCs during progressive stages differentiation. This revealed final...