A5016686300- Renal and related cancers
- Renal cell carcinoma treatment
- Pluripotent Stem Cells Research
- Organ Donation and Transplantation
- Genetic and Kidney Cyst Diseases
- Amino Acid Enzymes and Metabolism
- Tissue Engineering and Regenerative Medicine
- Metabolism and Genetic Disorders
- Ion Transport and Channel Regulation
- Single-cell and spatial transcriptomics
- Neonatal Health and Biochemistry
- Cancer Genomics and Diagnostics
- Renal Transplantation Outcomes and Treatments
- Pancreatic function and diabetes
- Renin-Angiotensin System Studies
- Neuroscience and Neuropharmacology Research
- Energy Harvesting in Wireless Networks
- COVID-19 Clinical Research Studies
- Genetic Neurodegenerative Diseases
- Organ Transplantation Techniques and Outcomes
- Cytomegalovirus and herpesvirus research
- Hereditary Neurological Disorders
- Urological Disorders and Treatments
- Healthcare Systems and Public Health
- 3D Printing in Biomedical Research
Murdoch Children's Research Institute
2017-2024
The University of Melbourne
2018-2024
The University of Queensland
2011-2019
Centenary Institute
2007-2011
The University of Sydney
2007-2010
Protein absorption in the intestine is mediated by proteases and brush-border peptidases together with peptide amino acid transporters. Neutral acids are generated a variety of aminopeptidases carboxypeptidases subsequently taken up transporter B(0)AT1 (SLC6A19), which mutated Hartnup disorder. Coexpression carboxypeptidase angiotensin-converting enzyme 2 (ACE2) Xenopus laevis oocytes led to dramatic increase expression at oocyte surface. Other members SLC6 family were not stimulated...
Solute carrier family 1, member 1 (SLC1A1; also known as EAAT3 and EAAC1) is the major epithelial transporter of glutamate aspartate in kidneys intestines rodents. Within brain, SLC1A1 serves predominant neuronal buffers synaptic release excitatory neurotransmitter within interneuronal cleft. Recent studies have revealed that polymorphisms are associated with obsessive-compulsive disorder (OCD) early-onset patient cohorts. Here we report mutations leading to substitution arginine tryptophan...
Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population embryonic kidney gives rise all cells within other than collecting duct through mesenchyme-to-epithelial transition, but this is exhausted around time birth. Here, we sought identify conditions under which adult proximal tubule could be directly transcriptionally reprogrammed progenitors. Using combinatorial screen for lineage-instructive...
While pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification metanephric progenitors results in elongated and radially aligned proximalised nephrons distinct S1 - S3 tubule cell types. Such PT-enhanced possess improved albumin...
Iminoglycinuria (IG) is an autosomal recessive abnormality of renal transport glycine and the imino acids proline hydroxyproline, but specific genetic defect(s) have not been determined. Similarly, although related disorder hyperglycinuria (HG) without iminoaciduria has attributed to heterozygosity a putative defective glycine, proline, hydroxyproline transporter, confirming underlying difficult. Here we applied candidate gene sequencing approach in 7 families first identified through...
Amino acid uptake in the intestine and kidney is mediated by a variety of amino transporters. To understand role epithelial neutral whole body homeostasis, we analyzed mice lacking apical broad-spectrum (0) transporter B(0)AT1 (Slc6a19). A general aminoaciduria was observed similar to human Hartnup disorder which caused mutations SLC6A19. Na(+)-dependent acids into renal brush-border membrane vesicles abolished. No compensatory increase peptide transport or other transporters detected. Mice...
Abstract Background While single-cell transcriptional profiling has greatly increased our capacity to interrogate biology, accurate cell classification within and between datasets is a key challenge. This particularly so in pluripotent stem cell-derived organoids which represent model of developmental system. Here, clustering algorithms selected marker genes can fail accurately classify cellular identity while variation analyses makes it difficult meaningfully compare datasets. Kidney...
With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets cells to directly impact renal function, or damage is primarily an indirect outcome. To date, several studies have utilized organoids understand the pathogenesis COVID-19, revealing ability for predominantly infect proximal tubule (PT), with reduced infectivity following administration soluble ACE2. However, immaturity standard...
The generation of reporter lines for cell identity, lineage, and physiologic state has provided a powerful tool in advancing the dissection mouse kidney morphogenesis at molecular level. Although use this approach is not an option studying human development vivo, its application induced pluripotent stem cells (iPSCs) now feasible.We used CRISPR/Cas9 gene editing to generate ten fluorescence iPSC designed identify nephron progenitors, podocytes, proximal distal nephron, ureteric epithelium....
Renal maturation occurs post-natally in many species and reabsorption capacity at birth can vary substantially from the mature kidney. However, little is known regarding of amino acid transport mechanisms, despite well-known physiological state developmental iminoglycinuria. Commonly seen during early infancy, iminoglycinuria a transient version persistent inherited form disorder, referred to as iminoglycinuria, manifests urinary hyperexcretion proline, hydroxyproline glycine. The...
T cell-mediated rejection of kidney allografts causes epithelial deterioration, manifested by tubulitis, but the mechanism remains unclear. We hypothesized that interstitial inflammation triggers a stereotyped response similar to triggered other types injury such as ischemia-reperfusion. identified solute carrier transcripts with decreased expression in mouse allografts, and compared their behavior native kidneys ischemic acute tubular necrosis (ATN). Average loss was ATN (77%) (75%) high...
Human pluripotent stem cells, after directed differentiation in vitro, can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation also reform embryonic organ structure tissue disruption. It has previously been demonstrated that dissociated kidneys recreate epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here we investigate timing underlying mechanisms driving dissociation using time-lapse imaging,...
Abstract Recent advances in the directed differentiation of human pluripotent stem cells to kidney brings with it prospect drug screening and disease modelling using patient-derived cell lines. Development such an approach for high content will require substantial quality control improvements throughput. Here we demonstrate use NovoGen MMX 3D bioprinter generation highly reproducible organoids from as few 4,000 cells. Histological immunohistochemical analyses confirmed presence renal...